1 BTS Clinical Statement on Air Travel for Passengers with Respiratory Disease

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4 Draft for public consultation

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6 Available for public consultation from Monday 13 January to Monday 10

7 February 2020

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12 Contact:

13 British Thoracic Society,

14 17 Doughty St, London WC1N 2PL

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16 [email protected]

17 A response form is available on the BTS website.

18 Please send your responses to Sally Welham by 5pm on Monday 10 February

19 2020

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22 BTS Clinical Statement on Air Travel for Passengers with Respiratory Disease 23 24 AUTHORS 25 Robina Coker, Alison Armstrong, Colin Church, Steve Holmes, Jonathan Naylor, Katy Pike, Peter 26 Saunders, Kristofer Spurling, Pamela Vaughn on behalf of the British Thoracic Society 27 28 CONTENTS PAGE 29 Introduction 3 30 Scope 4 31 Methodology 5

32 Glossary 6

33 Pre-flight screening 7

34 Infants and children: special considerations 9

35 Hypoxic challenge testing 11

36 Disease/condition-specific advice with clinical practice points 16 37 Chronic airflow obstruction including asthma and COPD 38 Cystic fibrosis 39 Interstitial lung disease 40 Thoracic surgery and other interventional procedures 41 Pleural disease 42 Respiratory infections 43 Obstructive sleep apnoea syndrome 44 Respiratory muscle and chest wall disorders 45 Venous thromboembolism 46 Pulmonary hypertension 47 Lung cancer and mesothelioma 48 Hyperventilation and dysfunctional breathing 49

50 Disclaimer

51 Declarations of interest

52 Appendices

53 1. Practical considerations and useful sources of information 54 2. Logistics of air travel with equipment 55 3. Technical information for respiratory physiologists 56 4. Example of patient information leaflet – not included in consultation draft

57 References 45

58

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59 Introduction

60 BTS recommendations for managing passengers with stable respiratory disease planning air travel 61 were published in Thorax in 2011 (1). This followed original guidance published in 2002 (2) and an 62 online update in 2004 (3). The 2011 recommendations provided an expert consensus view based on 63 literature reviews, aimed at providing practical advice for lung specialists in secondary care. 64 Recognising that our knowledge in this area has grown since 2011 and that updated pragmatic advice 65 regarding respiratory disease and air travel is now required, the Society commissioned a new Clinical 66 Statement in 2018. 67 68 Although air travel appears generally safe for passengers with respiratory disease previously assessed 69 by a lung specialist (4), a decision to undertake air travel cannot always be taken lightly. Diverted 70 flights incur significant expense and inconvenience, and a patient who deteriorates in mid-air can pose 71 huge challenges to airline crew and other passengers. High altitude destinations can also be 72 problematic. 73 74 Regulatory governmental agencies require aircraft cabin pressure to simulate an altitude of 2438 m 75 (8000 ft cabin altitude) and allow only short diversions to a cabin altitude of 3048 m (10 000 ft) for 76 safety reasons (IATA 2018). The choice of 2438 m was based on the oxy-haemoglobin dissociation

77 curve, which shows that up to this level arterial oxygen saturations (SaO2) remain > 90% in the average 78 healthy individual (5). 79 80 In addition to the passenger’s respiratory condition and significant co-morbidities, a decision 81 regarding suitability for air travel should consider flight duration, destination (especially if at altitude 82 or subject to extreme weather conditions), equipment and medications, and whether equipment will 83 operate effectively and safely at altitude. 84 85 There have been developments in three key areas over the last decade. The first is an attempt, with 86 research from several groups, to define more precisely the value and role of the hypoxic challenge 87 test (HCT). This has included examining the accuracy of other, more routinely available lung function 88 parameters, in predicting hypoxaemia during air travel. HCT can be expensive in terms of equipment 89 and consumables, and demands additional resource in terms of staff time. A ‘negative’ HCT (where 90 in-flight oxygen is deemed not to be required) will take 20 minutes excluding preparation; if oxygen 91 titration is needed it will take a minimum of 40 minutes. Spirometry requires 20 minutes, a walk test

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92 30 minutes, and ‘full’ lung function testing 45 minutes (6). Furthermore, recent spirometry, walk tests 93 and other parameters may already be available for patients as part of their routine clinical care. 94 95 The second development, following from this, has been increasing recognition that, although early 96 research in this area focused on patients with COPD, other patient groups may behave differently in 97 terms of their response to altitude-related hypoxaemia. Although data remain limited, it does appear 98 that a ‘one size fits all’ approach is no longer supported by the available evidence. 99 100 Finally, the equipment used to deliver oxygen has changed significantly over the last decade, with 101 much greater availability of portable oxygen concentrators (POCs). For overseas travel, patients 102 usually need to lease a POC privately, since UK companies do not generally allow their equipment to 103 be taken out of the country. If a POC is to be used in-flight, the equipment must be approved by the 104 airline in advance. There are now a wide variety of such devices, providing varying flow rates and 105 modes of delivery (continuous flow versus pulsed-dose), and not all are suitable for all individual 106 patients. Revised, clear advice on the logistics of air travel for patients requiring oxygen is therefore 107 now essential. 108 109 Attention has therefore been drawn in this Statement to newer data, especially those published 110 since the 2011 BTS recommendations (1). Readers wanting more detailed background information 111 on physiology and the flight environment should consult the 2002 and 2011 BTS documents (1, 2).

112 Scope 113 The Clinical Statement provides practical advice for healthcare professionals in primary and secondary 114 care managing passengers with lung disease planning commercial air travel, including those 115 recovering from an acute event/exacerbation. It provides information for patients and carers, also 116 intended to be helpful to patient support groups, airlines and associated medical services. 117 118 The Statement addresses adults and children with the following conditions or undergoing the 119 following procedures: 120 • Airflow obstruction including asthma and COPD 121 • Bronchopulmonary dysplasia 122 • Cystic fibrosis 123 • Restrictive respiratory disease including ILD, respiratory muscle and chest wall disorders 124 • Thoracic surgery or other interventional procedures 125 • Pleural disease including pneumothorax and pleural effusion

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126 • Respiratory infections 127 • Obstructive sleep apnoea syndrome 128 • Venous thromboembolism 129 • Pulmonary hypertension 130 • Lung cancer and mesothelioma 131 • Hyperventilation and dysfunctional breathing 132 133 Pre-flight assessment is described. Appendices provide information for patients; logistics on air travel 134 with equipment (nebulisers, oxygen and ventilators); and technical information for respiratory 135 physiologists. 136 137 Heart disease and HIV are excluded, as are emergency repatriation and travel on military or other non- 138 commercial flights including helicopter travel. The Terrence Higgins Trust and British Heart 139 Foundation provide advice on travel with HIV and heart conditions respectively (see Appendix 1). 140 141 Methodology 142 Dr Robina Coker chaired the Clinical Statement Group (CSG). Membership was drawn from respiratory 143 medicine, paediatrics, nursing, respiratory physiology, physiotherapy and primary care. The CSG 144 identified key areas requiring Clinical Practice Points. The group reviewed previous BTS 145 recommendations on this topic (1) and supplemented the evidence with up to date literature 146 searches. The overall content was developed to reflect the scope approved by the BTS Standards of 147 Care Committee. Following discussions of broad statement content, individual sections were drafted 148 by group members. A final edited draft was reviewed by the BTS SOCC before posting for public 149 consultation and peer review on the BTS website January 2020. The revised document was re- 150 approved by the BTS Standards of Care Committee in TBC before final publication. 151

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152 Glossary 153 CF Cystic Fibrosis

154 COPD Chronic Obstructive Pulmonary Disease

155 CPET Cardiopulmonary Exercise Testing

156 CPAP Continuous Positive Airway Pressure

157 DOAC Direct Oral Anticoagulant

158 DVT Deep Vein Thrombosis

159 HCT Hypoxic Challenge Test

160 ILD Interstitial Lung Disease

161 LMWH Low Molecular Weight Heparin

162 PE Pulmonary Embolism

163 POC Portable Oxygen Concentrator

164 SARS Severe Acute Respiratory Disorder

165 SWT Shuttle Walk Test

166 VTE Venous Thromboembolism

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167 Pre-flight screening 168 Why? 169 A medical emergency occurs in 1 of 604 flights and 1 in 30, 000 passengers (7, 8). Respiratory illnesses 170 comprise around 12% of in-flight emergencies; others include syncope (37.4%), cardiac symptoms 171 (7.7%), stroke (2%) and cardiac arrest (0.3%). In a recent study of 1260 healthy volunteers, no

172 significant changes occurred in pulse oximetry (SpO2) during a simulated 8 h flight (9). However, if

173 flight altitude exceeds 3048 m (10 000 ft), hypoxaemia becomes more prominent and SaO2 falls to 174 89% in healthy individuals (10).

175 ∼ 176 Other potential risks posed by air travel include low relative humidity, and altitude-related expansion 177 of gases within enclosed pulmonary parenchymal spaces according to Boyle’s law. At a cabin altitude 178 of 2438 m (8,000 ft) this results in a 38% expansion of humidified gas. 179 180 Who? 181 There is no good quality evidence to determine who should have a formal assessment before air travel. 182 Experts generally advise pre-assessment or screening for the following adults, children and infants: 183 a. Those with a respiratory condition with the potential to deteriorate acutely resulting 184 in incapacitation and/or the need for medical intervention. This includes (but is not 185 exclusive to): 186 i. Severe (FEV1 < 50% predicted (11) or poorly controlled obstructive airway 187 disease (evidenced by symptoms, oxygen requirements, severe and/or 188 frequent exacerbations) 189 ii. Symptomatic restrictive lung or chest wall conditions, or known respiratory 190 muscle weakness causing breathlessness and exercise limitation 191 iii. Pulmonary hypertension 192 iv. Co-morbid conditions which may be worsened by hypoxaemia 193 (cerebrovascular or cardiac disease) 194 v. Recent (< 6 weeks) hospital treatment for a respiratory condition 195 vi. Requirement for CPAP or ventilatory support such as NIV 196 vii. Active cancer with lung involvement 197 viii. Patients already requiring LTOT or other oxygen 198 b. Recent (< 6 weeks) pneumothorax 199 c. Recent (< 6 weeks) pulmonary embolus or deep venous thrombosis, or increased risk 200 of venous thromboembolism (VTE)

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201 d. Anyone who has experienced significant symptoms during previous air travel, or 202 whose condition is of concern to their physician 203 204 The following are generally considered contra-indications to air travel: 205 a. Untreated ventilatory failure 206 b. Untreated pneumothorax 207 c. Respiratory infection representing a risk to others e.g. TB, SARS, MERS 208 d. Bronchogenic cysts. Cerebral air embolism, in some cases fatal, has been reported 209 in aircraft passengers after rupture of a bronchogenic cyst (12). 210 211 Patients with severe hypoxaemia requiring >4 L/min oxygen were previously advised against air travel, 212 because 4L/min was the maximum fixed flow rate routinely available on commercial aircraft. With 213 increasing availability of flight-approved POCs delivering a wide range of continuous and intermittent 214 flow rates, this cut-off no longer applies. However, flow rates >5 L/min delivered by nasal cannulae 215 may lead to nasal dryness and epistaxis. 216 217 In-flight oxygen may be contra-indicated in adults and children with a history of type 2 respiratory

218 failure (13, 14). Hypoxic challenge with PaCO2 measurement was advised for this group in 1996 (10) 219 but there has been little research since. This document therefore follows the 2015 BTS Guideline for 220 Home Oxygen Use in Adults (15) when making recommendations for managing patients with 221 previously documented hypercapnia. 222 223 Clinical Practice Points 224 All patients should undergo initial evaluation with history and physical examination by an experienced 225 clinical practitioner. The history should include: 226 a. Review of symptoms, baseline exercise capacity, recent exacerbation history, 227 treatments and previous experience of air travel 228 b. Consideration of the logistics of the intended journey, to include (if known): 229 i. Number and duration of flights 230 ii. Aircraft type 231 iii. Airports including departure, stop-over and destination 232 iv. Time away from home 233 v. Return journey 234

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235 Further assessment by a Respiratory Specialist is advised for those in whom screening raises concerns, 236 and hypoxic challenge testing may be advised. 237 238 Infants and Children 239 In general, similar considerations apply to both adults and children if they have severe chronic airway 240 disease, or require chronic supplementary oxygen, or non-invasive or tracheostomy ventilation. Both 241 children and adults with these conditions require a pre-flight assessment. Similarly, unless otherwise 242 stated, recommendations for individuals with previous thoracic surgery, pneumothorax or empyema 243 apply to both adults and children. There are, however, some specific considerations for infants and 244 younger children since a number of factors place infants at greater risk of developing hypoxia. These 245 factors include left shift of the oxygen dissociation curve (due to the presence of fetal haemoglobin), 246 smaller airway diameter, relatively fewer alveoli, compliant rib cage and increased tendency to 247 pulmonary vasoconstriction and bronchoconstriction and thus ventilation–perfusion mismatch under 248 hypoxic conditions. Moreover, preterm infants and infants under two months of age may develop 249 apnoea/hypoventilation in response to hypoxia or infection(16, 17) . 250 In addition to very young and ex-preterm infants, the children most at risk of hypoxia are those with 251 anaemia, a cardiac condition, neuromuscular disorders, or chronic or acute lung disease. Low humidity 252 during air travel can also present a problem for children with respiratory conditions such as cystic 253 fibrosis. Those most at risk of complications associated with reduced air pressure are children with 254 upper respiratory tract infections, or trapped intrathoracic air, including those with recent 255 pneumothorax or cystic lung disease (18). 256 The following Clinical Practice Points are specific to infants and children. 257 258 Clinical Practice Points 259 260 • For infants born at term (>37 weeks) it is prudent to delay flying for 1 week after birth to 261 ensure they are healthy (19). 262 • In view of their greater risk of apnoea and hypoxia, infants born prematurely (<37 weeks) with 263 or without a history of respiratory disease who have not reached their expected date of 264 delivery should have in-flight oxygen available. HCT may not be a reliable guide of oxygen 265 requirement in this group (20). If air travel is essential, they should travel with oxygen at a 266 tolerable low flow, recognising that for many airlines this will be 1 l/minute 267 • Infants under 1 year with a history of chronic respiratory problems should be discussed with

268 a respiratory paediatrician and HCT considered. Those with SpO2 <85% on HCT should have

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269 in-flight oxygen available; paediatrician discretion should be used for infants with SpO2 85- 270 90% recognising that sleep or respiratory infection may further reduce saturations in this 271 group.

272 • In children with chronic lung disease able to perform spirometry whose FEV1 is consistently 273 <50% predicted, HCT should be considered. This includes children with cystic fibrosis. Children 274 with chronic lung disease who are too young to reliably perform spirometry should have a 275 clinical assessment of assess disease severity and their likely tolerance of hypoxia. For children 276 with cystic fibrosis the disease is rarely severe enough to compromise lung function 277 significantly at this age. 278 • Infants and children who have required long-term oxygen in the last 6 months should be 279 discussed with a respiratory paediatrician and HCT considered. 280 281 How? 282 Pulse oximetry is the easiest and usually first screening test (4). It has generally been accepted in the

283 past that those with resting SpO2 >95% at sea level should not require in-flight oxygen (2, 19, 21-24). 284 Spirometry is usually advised in patients with known acute or chronic lung disease, or with symptoms 285 suggesting lung disease (25, 26). However, lung function parameters are in many cases poor at 286 predicting hypoxaemia or complications (22, 27-29). 287 288 Historically, those able to walk 50 m or climb 10–12 stairs without distress have been considered to 289 have sufficient cardiopulmonary reserve to fly (2, 30). The role of the six minute walk test (6MWT) in 290 pre-flight evaluation, widely used to assess functional capacity and exercise-induced hypoxaemia in 291 COPD (31-34) and ILD including IPF (35-37), has also been examined. 292 293 Current data suggest that the 50 m walk test is an insensitive assessment of ‘fitness to fly’ (38), 294 although still sometimes referenced by airlines and aviation authorities (30, 39, 40). Several studies 295 show no correlation between walking distance and HCT outcome in patients with COPD, ILD or extra- 296 pulmonary restriction (32, 38, 41, 42). One study showed no correlation between exertional dyspnoea 297 and HCT outcome (32). The 50 m walk test alone thus appears unsuitable for pre-flight assessment. 298 299 The 6MWT and externally-paced incremental shuttle walking test (SWT) may however be of value. 300 Baseline values do not reliably predict in-flight hypoxaemia in a number of respiratory conditions (1, 4,

301 27, 28, 41, 43-45) but changes in SpO2 during 6MWT and SWT may correlate with HCT outcome in

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302 COPD, ILD and chest wall deformity (24, 32, 41, 42). Walk tests cannot predict the in-flight oxygen 303 flow rate required; they may however inform the decision as to who needs further assessment. 304 305 Hypoxic Challenge Testing 306 Hypoxic challenge testing is performed using an inspired gas mixture containing 15% oxygen, which

307 gives an approximate similar inspired oxygen tension (PO2) to breathing air at the maximum allowable 308 cabin pressure altitude (2,438m, or 8,000ft)(46, 47). Hypoxic challenge testing is usually performed in 309 a specialist respiratory physiology unit. The provision of a 15% oxygen gas mixture can be achieved 310 using one of the methods described in Appendix 3. 311 312 The closest approximation to aircraft cabin conditions entails exposure to simulated altitude in a 313 hypobaric chamber, but such chambers are not available for clinical assessment. A reasonable 314 substitute is the normobaric hypoxic challenge test (HCT), described by Gong in 1984 (48) in patients 315 with chronic airflow obstruction. This assesses the response to hypoxaemia achieved by breathing a 316 hypoxic gas mixture at sea level. Various methods of hypoxic gas delivery produce equivalent results 317 to tests in a hypobaric chamber or during real flights in adults with COPD (1, 33, 49-51). Data are 318 limited in other conditions as well as for children and neonates. 319 320 The HCT is used to help decide whether passengers with respiratory disease need in-flight oxygen and 321 at what flow rate. It does not assess fitness for air travel, despite its reputation as a ‘fitness to fly’ 322 test. If healthcare providers perpetuate this impression in patient information, they must manage 323 patient and carer expectations accordingly. A ‘pre-flight oxygen test’ is a more accurate description. 324 Most patients do not require HCT as part of pre-flight medical assessment, and there should not be 325 pressure on physicians to arrange, or healthcare professionals to perform, unnecessary HCT. 326 327 The physiological response to hypobaric hypoxia (PaO2 < 8 kPa) is increased ventilation (52). 328 Alterations in respiratory pattern may adversely impact on lung mechanics (53), which may be further 329 impaired by gas expansion, reducing vital capacity and increasing residual volume (54). The increase 330 in ventilatory drive is likely to be limited on commercial flights (55), but a modest increase in 331 ventilation can exhaust an already reduced ventilatory reserve (12, 53, 56). 332 333 The usual consensus is to recommend in-flight oxygen if PaO2 is predicted to fall below 6.6 kPa (50 334 mm Hg) or SpO2 below 85% in flight. There is little high quality evidence supporting these cut-off 335 values, but this PaO2 value ensures that SpO2 remains above the steep portion of the oxy-

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336 haemoglobin dissociation curve (57). Some authors consider 6.6 kPa to represent severe hypoxaemia 337 (39); pulmonary vascular resistance (PVR) increases sharply in response to arterial pO2 below this level 338 (20), with the potential for an acute increase in right ventricle afterload and right ventricular 339 dysfunction (40). As many patients with COPD have cardiac comorbidity (58), hypoxaemia in these 340 patients could precipitate cardiac ischemia, but this is unlikely in those with stable disease and good 341 exercise tolerance (59) (60). In the absence of new evidence to the contrary, the cut-off PaO2 of 6.6 342 kPa during HCT appears reasonable. 343 344 HCT outcomes do not predict respiratory symptoms during air travel (61) (62) (63). Such symptoms 345 do not appear to result directly from hypoxaemia (55), but from a combination of poor respiratory 346 mechanics and reduced respiratory reserve impairing the response to hypoxaemia. Symptoms are 347 more likely to occur in those with more severe breathlessness at sea level (4, 62). Limited evidence 348 suggests that those who desaturate during HCT and have previously experienced respiratory 349 symptoms during air travel can avoid these by using in-flight oxygen (23, 61). Symptoms may also 350 result from anxiety regarding air travel (see section on hyperventilation and dysfunctional breathing). 351 352 Patient selection for HCT 353 Those with stable respiratory disease without history of air travel intolerance, resting hypoxaemia at 354 sea level or significant cardiac comorbidity are unlikely to need in-flight oxygen and should not require 355 HCT. Those having had HCT in the past should not need the test repeated unless there is a change in 356 the patient’s clinical condition, but the patient’s plans should be discussed with the patient’s 357 respiratory physician, paediatrician or specialist nurse. Those already on home oxygen therapy will 358 need in-flight oxygen. Ideally, the flow rate required at cruising altitude should be determined using 359 HCT. If HCT is not available and there are no concerns about hypercapnia, passengers already on LTOT 360 should be advised to double the flow rate at cruising altitude provided the equipment is able to 361 provide it. However POCs do not ordinarily provide continuous flow rates above 3 L/min, and the 362 pulse-dose delivery mode provided at higher levels may not be suitable (64) . 363 364 Work by Edvardsen and colleagues in a cohort of 100 COPD patients suggests that desaturation below

365 84% SpO2 predicts a need for in-flight supplementary oxygen (24). They conclude that COPD patients with 366 baseline SpO2 >95% and exercise desaturation to no less than 84% on 6 MWT can fly without further 367 assessment and do not require in-flight oxygen (24). After prospective analysis of a smaller COPD 368 cohort (n=50) they further suggest that patients with resting sea level SpO2 92-95% who desaturate 369 below 84%, or who have resting sea level below 92%, should have in-flight oxygen made available and

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370 do not require HCT. It should be noted that none of this cohort apparently demonstrated hypercapnia, 371 and that the default flow rate for in-flight oxygen supplied on board aircraft in 2012 was 2L/min. It 372 would be valuable to have these data confirmed in a different cohort of COPD patients without 373 hypercapnia. 374 375 Some data are also available in smaller numbers of patients with restrictive lung disease, but there is 376 currently no consensus regarding the best walk test or cut-off values to use. In a study of 14 patients 377 with primary thoracic scoliosis, Bandyopadhyay and colleagues found that resting SpO2 >95% did not 378 accurately identify those who do not desaturate during HCT, and recommend a low threshold for 379 performing HCT on patients with thoracic scoliosis (41). Likewise, in a study of 13 patients with obesity 380 hypoventilation syndrome, baseline SpO2 did not predict HCT outcome (43). In a study including 42 381 patients with interstitial lung disease (ILD) and 20 with extra-pulmonary restriction (29) before and 382 after ‘two minutes of moderate exercise’, Ling and colleagues proposed that a post-exercise SpO2 of 383 no less than 95% could be used to exclude the need for HCT. Further research is required to determine 384 the most appropriate assessments for patients with a variety of restrictive lung diseases, including 385 which (if any) can reliably eliminate the need for HCT. 386 387 Clinical Practice Points: patient selection for HCT 388 389 The following should not require HCT: 390 • Those with stable disease who have previously undergone HCT (no recent hospital admissions, 391 exacerbations, or significant changes to treatment) 392 • COPD patients with baseline SpO2 >95% and desaturation to no less than 84% during 6MWT 393 should be able to travel without in-flight oxygen 394 • Those with previous significant intolerance to air travel, such as mid-air emergency oxygen or 395 diversion. These should have in-flight oxygen available at 2 L/min provided there is no history 396 of hypercapnia 397 398 HCT should be considered for the following:

399 • COPD patients with resting SpO2 ≤95% or desaturation to < 84% on 6MWT 400 • Infants and children with a history of neonatal respiratory problems, or existing severe chronic 401 lung disease including those with FEV1 persistently < 50% predicted (see page 7)

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402 • Adults and children with severe asthma, evidenced by persistent symptoms and/or frequent 403 exacerbations despite optimal treatment (see BTS/SIGN Asthma Guideline (65)) regardless of

404 resting sea level SpO2

405 • Patients with moderate or severe restrictive disease, including those in whom SpO2 falls to

406 <95% on exercise, and/or in those in whom either TLCO ≤ 50% or resting sea level PaO2 ≤9.42 407 kPa (see page 17) 408 • Those with existing or previous hypercapnia and those at risk of hypercapnia, including those 409 taking medication(s) which can cause respiratory depression 410 • Patients already on LTOT at sea level. However, if HCT is not available and there is no evidence 411 of hypercapnia, it seems reasonable to recommend that the oxygen flow rate is doubled at 412 cruising altitude, provided the equipment is able to provide it (see Appendix 2). 413 414 Clinical Practice Points: HCT results

415 • PaO2 ≥ 6.6 kPa (≥ 50 mm Hg) or SpO2 ≥ 85%: in-flight oxygen not required

416 • PaO2 < 6.6 kPa (<50 mm Hg) or SpO2 <85%: in-flight oxygen recommended

417 • Where required, titrate oxygen to maintain PaO2 ≥ 6.6 kPa or SpO2 ≥ 85% 418 419 Air travel may be contraindicated in infrequent cases when supplementary oxygen, at the flow rate 420 needed to maintain PaO2 ≥6.6 kPa or SpO2 ≥ 85%, causes significant changes to pH and pCO2. The 421 2015 BTS Guidelines for home oxygen use in adults guidelines (15) consider that a pH<7.35, and pCO2 422 increase >1 kPa from baseline is significant. Specialist respiratory physicians should use discretion to 423 determine the risk in individual cases and advise accordingly. Where hyperventilation is suspected, 424 especially in response to anxiety rather than hypoxaemia, results should be interpreted with caution 425 as there is a risk of false negative results (66). 426 427 HCT Methods 428 These are described in Appendix 3. 429 430 Exertion on board 431 Studies in adults with COPD (27, 67, 68) or cystic fibrosis (69) have shown that patients can develop 432 profound hypoxaemia when exercising under hypoxic conditions, whether on board a commercial aircraft 433 at cruising altitude or during HCT. This has been reported in patients whose resting HCT values would 434 otherwise not warrant oxygen; in some cases PaO2 values as low as 3.9 kPa have been recorded (27, 68). 435

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436 The combination of further hypoxaemia and increased ventilatory demand from exertion while flying 437 may challenge those already approaching the limits of their respiratory reserve. It therefore seems 438 prudent to recommend that passengers with significant respiratory limitation, regardless of whether 439 travelling with in-flight oxygen, should request an aisle seat near a toilet to avoid long periods of 440 walking (1, 23, 70). Passengers should keep active by undertaking seat-based exercises and/or 441 standing at intervals if flight conditions permit. Patients who cannot tolerate withdrawal of 442 supplemental oxygen for even a short period of time should not travel by air, as there will be periods 443 of time when oxygen cannot be supplied. 444 445

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446 Disease/condition specific advice

447 Chronic airflow obstruction including asthma and COPD 448 Most adults and children with well-controlled mild or moderate airflow obstruction and no other co- 449 morbidities should have no problem with commercial air travel, but they should be prepared for the 450 possibility of an exacerbation of their condition. Air travel presents a theoretical risk of bronchospasm 451 because of mucosal water loss due to low cabin humidity. 452 453 Asthma 454 While asthma is prevalent and has the potential to be life-threatening, most episodes are minor and 455 still associated with passengers not having their medication to hand (71, 72). 456 457 Most passengers with asthma will have relatively mild disease and do not require HCT. HCT should 458 however be considered for individuals with severe asthma regardless of baseline sea level oxygen 459 saturation. In a retrospective study of 37 adults with severe asthma (as defined in the BTS/SIGN 460 Asthma Guideline (65)) undergoing HCT, two thirds who fulfilled the criteria for in-flight oxygen on 461 HCT had baseline sea level oxygen saturations of >95% (73). 462 463 The role of HCT has not been studied in children with severe stable asthma. A study in 51 children 464 aged 2 to12 years requiring transient oxygen therapy during an acute asthma attack (SpO2 <92%) 465 showed that although 5% failed HCT within 24 hours of discontinuing oxygen therapy, all passed the 466 HCT when retested at 48 hours (74). 467 468 Clinical Practice Points 469 • All medications and spacer devices should be carried in hand luggage to mitigate the risk of 470 missing hold baggage 471 • Emergency medications, including salbutamol inhalers and spacers, must be immediately 472 accessible 473 • Individuals prescribed adrenaline auto-injectors should have these to hand 474 • For acute exacerbations on board, the passenger’s own bronchodilator inhaler (or airline 475 emergency kit inhaler if available) should be given, with a spacer if appropriate, and the dose 476 repeated until symptomatic relief is obtained

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477 • Those with severe asthma should consult their respiratory specialist beforehand and consider 478 taking an emergency supply of oral corticosteroid in their hand luggage in addition to their 479 usual medication 480 • Food allergy affects up to 8.5% of children and adults with asthma (75), and asthma is a risk 481 factor for severe or fatal anaphylaxis (76). Appropriate precautions for those affected include 482 wiping tray tables and hands, informing cabin crew of allergies and not eating during flights 483 or bringing known ‘safe’ foods from home (77). 484 485 COPD 486 Patients with COPD planning air travel need careful evaluation, not only because of their respiratory 487 disease, but also because of their high levels of co-morbidity (61, 78). 488 489 Respiratory symptoms in those with COPD are common during air travel, but Edvardsen and 490 colleagues have shown that HCT does not predict respiratory symptoms during air travel in patients 491 with moderate to very severe COPD (61). They suggest that exacerbation of co-morbidities such as 492 cardiovascular disease (the commonest cause of death in COPD) is the most threatening consequence 493 of severe hypoxaemia. This is consistent with data showing a risk of cardiac arrhythmias and ischaemic 494 chest pain in patients with COPD unable to respond to the physiological stressors of air travel (48, 60). 495 Work by Robson and colleagues shows that resting sea level saturations alone do not predict HCT 496 outcome (22). 497 498 Spirometry does not reliably predict hypoxaemia or complications in COPD (23). It seems prudent to 499 avoid air travel within 6 weeks of an exacerbation although there are few data to support this 500 recommendation. 501 502 Clinical Practice Points 503 • All medications and spacer devices should be carried in hand luggage to mitigate the risk of 504 missing hold baggage. 505 • Emergency medications, including salbutamol inhalers and spacers, must be immediately 506 accessible. 507 • For acute exacerbations on board, the passenger’s own bronchodilator inhaler (or airline 508 emergency kit inhaler if available) should be given, with a spacer if appropriate, and the dose 509 repeated until symptomatic relief is obtained.

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510 • A history of previous pneumothorax or bullous lung disease necessitates assessment by a 511 respiratory specialist to determine the potential risk of complications from reduced cabin 512 pressure. 513 • COPD patients are at greater risk of venous thromboembolism (VTE) as a direct consequence 514 of their underlying condition, as well as after an exacerbation. They should be advised 515 accordingly, especially if planning longer flights when the risk is further enhanced (see section 516 on VTE page 34) (79-81). 517 • Patients requiring long-term oxygen therapy should also plan for oxygen supplementation at 518 their destination (see Appendix 1) (23). 519 • It seems prudent to advise that those who have had a recent exacerbation of their condition 520 should not fly until their condition is stable and use of reliever therapy has returned to their 521 usual baseline. 522 523

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524 Cystic Fibrosis (adults and children) 525 The risks associated with air travel are greater for those with cystic fibrosis (CF) than for healthy

526 individuals (82). This is despite the fact that people with CF have been shown to tolerate PaO2 values 527 below 6.6kPa (50 mm Hg) for several hours without cardiac decompensation or cerebral symptoms 528 (83), do not usually have cardiovascular comorbidities, and are generally younger than patients with 529 other respiratory conditions. Hypoxaemia results mainly from ventilation/perfusion mismatch 530 attributable to chronic inflammation and mucus plugging. It is not clear which physiological values 531 measured at sea level best predict hypoxaemia or complications during flight. 532 533 In one study of 30 adults with CF undergoing HCT, four fulfilled the criteria for supplemental oxygen

534 (PaO2 < 6.6 kPa) at rest and a further 11 dropped below this threshold while walking slowly. Variables

535 obtained during CPET (including SpO2 and PaO2) showed a stronger correlation with arterial oxygen

536 tension during HCT than baseline SpO2 or spirometry (69). However, in children with CF the sensitivity

537 and specificity of pre-flight HCT have been reported as 20% and 99% (using a cut-off of SpO2 <90% 538 during HCT with FiO2 0.15), compared with 70% and 96% for spirometry (cut-off FEV1 <50% predicted) 539 (84). Combining spirometry and HCT increased sensitivity to 80%. Spirometry may therefore usefully 540 predict who may desaturate during flight, and a cut-off of FEV1 50% has been used to recommend 541 HCT. 542 543 Passengers with CF should drink adequate fluids to prevent dehydration resulting from low cabin 544 humidity. Salty snacks may be needed to replace salt lost in sweat. Hand hygiene and attention to 545 required vaccinations are recommended to minimise risk of infection. These measures are included 546 within recommendations from the European Centres of Reference Network for Cystic Fibrosis” 547 (ECORN-CF) project, endorsed by the European Cystic Fibrosis Society (82). These also advise checking 548 the relevant airline policy and levels of CF healthcare provision at the proposed destination before 549 travel (see Appendix 1). 550 551 Clinical Practice Points 552 • All medications and spacer devices should be carried in hand luggage to mitigate the risk of 553 missing hold baggage. 554 • Patients with CF under the age of 6 are likely to be well enough to fly at the paediatrician’s 555 discretion.

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556 • In those with CF who are old enough for spirometry and whose FEV1 is <50% predicted, HCT 557 is recommended. If SpO2 falls below the 90% cut-off, as outlined above, in-flight oxygen is 558 advised.

559 • In children with chronic lung disease able to perform spirometry whose FEV1 is consistently 560 <50% predicted, HCT should be considered. This includes children with cystic fibrosis. Children 561 with chronic lung disease who are too young to reliably perform spirometry should have a 562 clinical assessment of assess disease severity and their likely tolerance of hypoxia. For children 563 with cystic fibrosis disease is rarely severe enough to severely compromise lung function at 564 this age. 565 566

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567 Interstitial lung disease (ILD) 568 Like individuals with airflow limitation, patients with interstitial lung disease (ILD), including 569 pulmonary fibrosis, respond to hypoxaemia at altitude with increased heart rate and minute 570 ventilation. In severe disease the ability to increase minute ventilation is limited and the resulting 571 hypoxaemia may be marked. However, unlike COPD, where many patients appear to be able to 572 tolerate marked hypoxia (85), patients with ILD may have acute or subacute disease and be less able 573 to withstand marked hypoxia. There are fewer relevant studies available in ILD, and patient numbers 574 are smaller than in COPD studies. 575 Two studies in patients with ILD (n = 15 and 10 respectively) have shown that sea level oxygen 576 saturations do not reliably predict HCT outcome, and that oxygen saturations fall significantly after 577 light exercise performed under conditions of normobaric hypoxia (63, 86). These findings are 578 consistent with those from the UK Flight Outcomes Study (4), a prospective observational study of 431

579 patients including 186 with ILD. This showed that neither FEV1 nor sea level SpO2 reliably predict 580 desaturation at altitude. However, patients with ILD were more likely than others to require 581 unscheduled healthcare for respiratory events within 4 weeks of air travel. 582 583 In a study including 15 patients with ILD, Martin and colleagues found that predictive equations 584 overestimated the need for in-flight oxygen in patients with ILD, as they did for those with COPD and 585 CF (87). 586 More recently, Barratt and colleagues examined the predictive value of various parameters for HCT 587 outcome in 106 ILD patients (69 with IPF) (88). Only the combined parameters of TLCO >50% predicted 588 and sea level PaO2 > 9.42 kPa independently predicted a successful HCT outcome. From analysis of a 589 subset of 88 patients with a complete dataset available the authors propose a new pre-flight algorithm 590 for ILD patients with a sensitivity of 86% and specificity of 84%. In patients with both sea level PaO2 591 ≤ 9.42 kPa and TLCO ≤ 50% predicted, in-flight oxygen is recommended without recourse to HCT. For 592 patients in whom either TLCO ≤ 50% or PaO2 ≤9.42 kPa, HCT is advised. This promising approach 593 requires further validation in a larger, prospective cohort of ILD patients, preferably supported by 594 patient reported outcomes from actual flight(s). 595 596 Clinical Practice Points 597 • In patients with co-morbidity, including pulmonary hypertension and/ or cardiovascular 598 disease, attention should also be paid to the impact of air travel on these conditions 599 • Physicians may wish to consider HCT in those whom SpO2 falls to <95% on exercise, and/or in 600 those in whom either TLCO ≤ 50% or PaO2 ≤9.42 kPa (if available).

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601 Thoracic surgery and other interventional procedures 602 There is no high-quality evidence in this area and further research and/or data collection is needed. 603 The following are suggested time periods before which a medically unaccompanied commercial flight 604 can safely be undertaken after the specific thoracic interventions described below. The advice is 605 conservative. Shorter recovery periods may be appropriate in individual cases, but only if approved 606 by the doctor/surgeon carrying out the procedure. 607 608 It is also important to note that the potential risks of travel are not just those associated with a post- 609 procedure pneumothorax, but include wound infection and pain, which could require medical 610 attention at destination and would need approval by the travel insurer. 611 612 Thoracic surgery, including VATS procedures 613 UK-based surgeons in two centres (Papworth and Leicester) independently advise against non- 614 essential air travel for 4 weeks after removal of drains (Jon Naylor, personal communication). If air 615 travel is essential, a minimum delay of 2 weeks is advised, depending on the type of surgery and the 616 surgeon’s advice. 617 618 Clinical Practice Points 619 • The opinion of the surgeon or interventionalist should be obtained before the patient travels 620 by air. Patients, professionals and their carers should be aware that this may result in a delay 621 of 4 weeks for non-essential air travel and 2 weeks for essential air travel. 622 • Careful clinical assessment of the patient is required. This should include consideration of 623 their baseline status including co-morbidities, SpO2, post-procedure complications such as 624 infection and/or pain, flight duration and destination. 625 626 Percutaneous lung biopsy, pleural procedures (including thoracocentesis, medical thoracoscopy and 627 insertion of indwelling pleural catheter) 628 A North American study of 179 patients, who between them underwent 183 percutaneous 629 transthoracic needle biopsies, suggested that air travel was safe within 24 hours of procedure, even 630 in the 65 patients (35%) who developed a small, stable post-biopsy pneumothorax (89). Fifty (77%) of 631 them flew within 4 days of the final post-biopsy chest radiograph. During a brief telephone survey 632 after the flight, 14 (8%) reported worsening of pre-existing respiratory symptoms or new respiratory 633 symptoms. There were no reported events requiring in-flight medical attention or flight diversion. It 634 must be noted that these were short, internal North American flights over land, where diversion is

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635 relatively straightforward if required. The situation for a UK-based patient travelling on a long-haul 636 flight to the Middle East, USA, Far East or Australasia is very different. 637 638 Clinical Practice Points 639 • The opinion of the interventionalist should be obtained before the patient travels by air 640 • Careful clinical assessment of the patient is required. This should include consideration of 641 their baseline status including co-morbidities, SpO2, post-procedure complications such as 642 infection or pain, flight duration and destination. 643 • Patients with no pneumothorax seen on the post-procedure chest x-ray should wait for one 644 week before air travel. 645 • Patients with a pneumothorax seen on the post-procedure chest x-ray should wait for one 646 week after resolution on chest x-ray before air travel. 647 648 “Trapped lung” after drainage of pleural space 649 Only very limited data are available, from a report of two patients with a small chronic 650 pneumothorax (90). This suggests that such patients may be able to travel safely by air, but require 651 thorough clinical assessment, computed tomographic imaging and hypoxic challenge testing as a 652 minimum beforehand. 653 654 Clinical Practice Points 655 • The opinion of the interventionalist should be obtained before the patient travels by air 656 • Patients should be assessed carefully and advised on a case by case basis 657 • Patients should be clinically stable before air travel. 658 659 Bronchoscopic procedures 660 The risks associated with air travel are not only related to possible pneumothorax, but also to the 661 effects of sedation, exacerbation of pre-existing or new symptoms such as cough, hoarse voice 662 haemoptysis and dyspnoea, respiratory infection, and the consequences of arrhythmias observed 663 during the procedure. 664 665 Clinical Practice Points 666 • The opinion of the interventionalist should be obtained before the patient travels by air. 667 • Patients should be clinically stable before they travel.

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668 • For patients who have undergone interventional bronchoscopy including TBNA, TBB, EBUS 669 and endobronchial valve insertion, those with no pneumothorax seen on the post-procedure 670 chest x-ray should wait for one week before air travel. 671 • For patients who have undergone interventional bronchoscopy including TBNA, TBB and 672 EBUS, those with a pneumothorax seen on the post-procedure chest x-ray should wait for one 673 week after resolution on chest x-ray before air travel. 674 675 676

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677 Pleural disease 678 Pleural effusion 679 Patients with stable pleural disease and normal resting oxygen saturations should be able to fly 680 without further precautions. Those who have indwelling long term drainage catheters should be 681 encouraged to take a supply of drainage bottles for their time away. 682 683 In those with an acute pleural effusion, investigation should be delayed if air travel is planned within 684 two weeks, since intervention may increase the risk of pneumothorax. The risk of delaying 685 investigation should be discussed with the individual to determine whether travel plans can be 686 modified. 687 688 Pneumothorax 689 The prevalence of in-flight pneumothorax in passengers with existing lung disease appears low overall, 690 being zero in the UK Flight Outcomes Study (4). It increases however in those at increased risk: 3.6% 691 in a study of 276 patients with lymphangioleiomyomatosis (LAM) (91) and 9% within one month of air 692 travel in a retrospective survey of 145 patients with Birt-Hogg-Dubé syndrome (BHD) (92). 693 694 Most individuals with an untreated, closed pneumothorax should not travel by air. In exceptional 695 cases where the pneumothorax is long-standing and thought to present a low risk, secondary care 696 evaluation is strongly advised before travel. 697 698 In individuals with a treated pneumothorax, exposure to altitude poses a risk of recurrence. There is 699 however evidence to suggest that in the case of traumatic pneumothorax, air travel as early as 72 700 hours after chest drain removal with full lung inflation may be safe (93). A prospective observational 701 study of 20 patients with a small residual traumatic pneumothorax, exposed to hypobaric hypoxia for 702 2 hours suggested no significant clinical effects despite expansion of up to 171% (94). The data should 703 be interpreted with caution given the small numbers involved, the small size of the pneumothoraces, 704 and the limited duration of hypobaric exposure. 705 706 In those who have undergone thoracotomy and surgical pleurodeses, the recurrence rate is so low 707 that no subsequent restriction on travel is necessary (1). The recurrence rate has been reported to be 708 four times greater after video-assisted thoracoscopy (95), suggesting that this procedure may not be 709 as definitive. The risk of recurrence is greatest in those with pre-existing lung disease, cigarette 710 smokers and taller men (1).

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711 712 Clinical Practice Points 713 • It appears prudent to advise that air travel should ideally not occur within seven days of full 714 resolution on CXR. 715 • Those at higher risk of recurrent pneumothorax should be advised accordingly. 716 • Higher risk groups, including those with cystic lung disease such as LAM and Birt-Hogg-Dubé 717 syndrome, should be advised accordingly. 718 • Patients with a small long-standing pneumothorax thought to present a low risk should be 719 evaluated in secondary care before travel.

720 721

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722 Respiratory tract infections 723 Upper Respiratory Infection including otitis media and sinusitis 724 During air travel with acute infection of the upper airway, the main risks, which are unpredictable but 725 may reflect previous experience, are of pain and potential rupture of the tympanic membrane. Those 726 with significant symptomatic viral upper respiratory tract infection may wish to delay their travel 727 because of the risk of pain and disseminating infection to others. 728 729 Barotrauma, characterized by otalgia, is a consequence of inability to equilibrate the pressure 730 differential between the external and middle ear. This is usually more severe during landing than take- 731 off. Most passengers, including older children, can equilibrate the pressure through yawning, 732 swallowing, chewing or a Valsalva manoeuvre (for example pinching the nose and blowing). Infants 733 and young children may be unable to perform these manoeuvres, but swallowing may be encouraged 734 by drinking and is also more frequent when the child is awake and/or crying.

735 It has been estimated that 10% of adults and 22% of children may have changes to the ear drum after 736 a flight, although perforation is rare and symptoms usually resolve spontaneously (96, 97). 737 738 Historically, oral (and to a lesser extent topical) decongestants have been recommended for adults 739 with risk factors for sinus or middle ear barotrauma (1). The evidence is very weak, and there is no 740 evidence in children. Treatment with intranasal steroids (commenced at least a week before the flight) 741 can however improve symptoms, as for inflammatory rhinosinusitis. 742 743 Clinical Practice Points 744 • Passengers who develop sinus barotrauma after flying should receive topical and oral 745 decongestants as well as appropriate analgesia. 746 • If there is an allergic component, intranasal steroids and/or oral corticosteroids may be 747 considered. 748 • Symptoms and signs of barotrauma should have resolved before flying again; some 749 recommend plain radiography to ensure that mucosal swelling has settled. This usually takes 750 between one and six weeks. 751 • After an episode of acute otitis media it is usually recommended that patients should not fly 752 for two weeks.(96) 753 754 755

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756 Viral infections 757 Viral infections such as influenza may be spread between air travellers. The usual method of 758 transmission is via droplet spread, usually only within one metre of source. Viral DNA persists on 759 frequently touched surfaces at the airport and on board the aircraft, and may be transmissible through 760 touch (98). 761 762 In modern commercial aircraft, air is usually extracted, filtered via a HEPA filter and returned within 763 the same seating row, such that flow is not from front to back. This can change when on the ground; 764 prolonged ground wait times may increase the risk of infection transmission. Recent research shows 765 that the risk zone for contagion is not limited to within two rows of the index case, as previously 766 thought, but that spread is more random owing to movement through the cabin (99). In this study 767 the average passenger had contact with 44 other passengers. Overall however, the risk of 768 transmission of infection appears quite low. 769 770 Some respiratory tract infections may be more infectious than others. A review of passengers 771 travelling on a flight carrying a confirmed case of SARs reported 16 cases of severe acute respiratory 772 syndrome (SARS) developing in fellow passengers (100). Special attention should be paid to the 773 clearance of people wishing to fly who have respiratory tract symptoms during outbreaks of such 774 infections. During outbreaks of serious infectious respiratory tract disease, airport screening may be 775 employed and travellers with a fever may be refused travel by the airline. In cases of serious epidemics 776 such as Middle East Respiratory Syndrome (MERS), even urgent travel will be prohibited. 777 778 Clinical Practice Points 779 • Patients with highly contagious infections including measles, chickenpox, mumps, SARS or 780 MERS should not be allowed to travel until they are considered to be non-infectious. 781 782 Tuberculosis 783 The WHO provide comprehensive information about the risk of air travel with tuberculosis (101). Risk 784 is determined by two factors: whether acid fast bacilli are present on smears of respiratory samples 785 or a sputum smear is culture positive; and whether drug resistance is present. Patients with sputum 786 smear or culture positivity are considered potentially infectious. 787 788 789

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790 Clinical Practice Points 791 • Smear positive patients must not fly until they have provided two smear negative samples on 792 treatment. 793 • For those starting treatment for pulmonary tuberculosis where not all the information is yet 794 known, it is prudent to advise against air travel in the first two weeks. 795 • For those who are smear negative and have a fully sensitive organism, this is the timescale in 796 which they would be expected to be rendered non-infectious by treatment. 797 • For patients with multi drug resistant (MDR/XDR) tuberculosis, travel is prohibited until two 798 negative culture samples have been produced and there is clinical evidence of improvement 799 on treatment. 800 • Extra-pulmonary tuberculosis does not usually warrant additional precautions with regard to 801 air travel except in cases of meningeal tuberculosis, where consideration must be given to 802 intra-cerebral pressure during altitude exposure. 803 804 Pneumonia 805 Patients suffering from acute bacterial pneumonia present a low risk to other passengers. They are 806 however more likely to experience in-flight desaturation during flight. 807 808 Clinical Practice Points 809 • It appears prudent to advise that all but essential travel is postponed for 7 days in those who 810 have reduced baseline sea level SpO2. 811 812 813 814 815 816 817 818

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819 Obstructive Sleep Apnoea Syndrome (OSAS) 820 The most recent available guidance states that for patients with OSAS, the potential risks during 821 commercial airline travel are worsening hypoxaemia when asleep, and exacerbation of jet lag with 822 potential adverse effects on driving (1). 823 824 Data are sparse regarding risks for passengers with OSAS during air travel. Some evidence suggests 825 there is a risk of cardiovascular and other adverse events in this group when staying at high altitude 826 destinations. Hypobaric hypoxia can promote central apneas in addition to obstructive events, which 827 may cause tachycardia, cardiac arrhythmia, and systemic hypertension (102). It is not however clear 828 how quickly this response develops, and therefore whether the findings are relevant to air travel. 829 830 Using hypobaric chamber simulation testing, studies have shown that there is an association between 831 hypoxaemia, decreased sleep time and an increased frequency of hypopneas for patients with OSAS 832 who are acutely exposed to high altitude (103). There are further adverse effects on sleep and OSAS 833 if alcohol (104) or sedatives (105) are taken. 834 835 Many patients with OSAS are already established on Continuous Positive Airway Pressure (CPAP). 836 Some studies have shown that patients with OSAS have lower oxygen saturations at baseline and at 837 cabin altitude simulation than normal subjects (106). The changes are more marked in those with 838 severe OSAS. Use of CPAP at altitude is associated with decreased central sleep apnoea and increased 839 sleep efficiency (103). 840 841 Consideration must be given to the whole journey. This is especially important if the flight involves 842 an overnight element and patients expect to drive the next day. Studies have identified that not using 843 CPAP for one night during the flight increases the risk of drowsiness at destination the following day 844 (107). 845 846 Careful planning is required. A retrospective survey of 394 patients who undertook air travel on CPAP 847 reported that over a third encountered problems with their equipment, power cord, adapter or 848 transport of the CPAP machine (101). These findings highlight the need for clinical teams to 849 understand the logistics in order to support safe patient travel (see Appendix 2 for further details). 850 851 In summary, the potential physiological risks for this group include cardiac stress, increased frequency 852 of hypopnoeas, possible central apnoeas, hypoxaemia and exacerbation of jet lag.

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853 • Clinical Practice Points 854 • Daytime flights are advised wherever possible. 855 • Careful planning and preparation is required, and use of the patient’s own CPAP device is 856 advised. 857 • Alcohol and sedatives should be avoided in the 12 hours before, and during, airline travel. 858 • Patients should use their CPAP device on board if they are travelling overnight, and avoid 859 sleeping during daytime flights. 860 • Consideration should be given to device settings and whether adjustment is required for 861 operation at altitude. 862 • Airline approval for carriage and use of device, including battery specification, must be gained 863 before travel. 864 • Consideration should be given to the whole journey. If driving is required the following day, 865 an overnight stay at destination may be advisable. 866 867 Respiratory muscle and chest wall disorders 868 There is little good evidence to guide decision-making around the need for oxygen or non-invasive 869 ventilation during air travel for patients with severe extra-pulmonary restriction resulting from chest 870 wall disorder or respiratory muscle weakness. One case report suggests that a long-haul flight may 871 have precipitated a first episode of pulmonary hypertension and right heart failure requiring 872 intubation and ventilatory support in a 59 year old man with congenital kyphoscoliosis and apparently 873 stable cardiorespiratory function before travel. FVC was documented as 0.98L on recovery (108). 874 875 Some work has been conducted to understand which patients require HCT. The authors of a study of 876 21 adults with idiopathic kyphoscoliosis or neuromuscular disease (109) concluded that those with 877 FVC < 1 litre, even with resting SpO2 > 95%, are likely to desaturate significantly at cabin altitude. 878 879 Since the 2011 BTS recommendations (1), several studies have tried to identify factors that may 880 predict the need for in-flight oxygen for patients with neuromuscular disease. One study aimed to 881 identify parameters that predict HCT outcome in 40 patients with MND. Baseline PaCO2 was the only 882 independent predictor of hypoxaemia during HCT (110). This appears to be supported by a more 883 recent study examining baseline PaCO2 as a predictor of HCT outcome (111). Patients likely to fail HCT 884 have a higher baseline PaC02, but the authors were unable to determine an absolute threshold PaC02 885 value that could identify patients needing in-flight supplementary oxygen. 886

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887 Another study in 36 patients with MND examined baseline lung function as a predictor of hypoxaemia 888 in response to altitude simulation (112). The authors concluded that Maximum Inspiratory Pressure 889 (MIP) and sea level SpO2 may help identify MND patients who will develop hypoxaemia at altitude. 890 Despite the small numbers, none of the patients with a MIP > 30 mmHg or with sea level SpO2 > 96% 891 desaturated below 85% during HCT. 892 893 Preliminary data from a smaller study of 12 patients with MND, the conclusion was that Sniff Nasal 894 Inspiratory Pressure (SNIP) may more accurately predict the risk of hypoxia during air travel in those 895 with neuromuscular disease and respiratory muscle weakness (113). 896 897 While evidence to date addresses specific patient groups, the principles may be applied to any 898 individual with a restrictive disorder resulting from respiratory muscle weakness or chest wall 899 deformity. Further research on the value of FVC, PaCO2, MIP and/or SNIP in predicting HCT outcome 900 in this group is desirable. In the meantime, it seems reasonable to recommend that individuals with 901 severe respiratory muscle weakness or chest wall deformity (FVC < 1 L) should undergo HCT before air 902 travel. Physicians should use their discretion for considering HCT if there are additional reasons for 903 concern, such as a history of previous travel intolerance, hypoxemia or hypercapnia. 904 905 In those with respiratory muscle weakness, the possibility of respiratory failure should also be 906 considered. For patients established on NIV, further planning and advice are required to support the 907 use of NIV during flight. If continuous flow oxygen cannot be provided by the airline or by POC, oxygen 908 and NIV cannot be used simultaneously. A decision around whether NIV or supplementary oxygen is 909 of greatest physiological importance to the patient is then required on an individual basis. The 910 previous travel history, current clinical condition and the presence or absence of overnight travel 911 should also be considered. (see Appendix 2). 912 913 In summary, the potential physiological risk for patients with restrictive respiratory disease is 914 respiratory failure resulting from inadequate ventilation. It is therefore essential to assess ventilatory 915 requirements before deciding whether supplementary oxygen is required. The risk of respiratory 916 failure must be understood and assessed before travel, and there are currently no absolute predictors 917 to guide which patients are likely to require supplementary oxygen. 918 919 920

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921 Clinical practice points: 922 • HCT is recommended for all patients with FVC < 1 L, pending further data, and may be 923 considered in others thought to be at particular risk. 924 • Patients should be advised to take daytime flights where possible. 925 • Further planning and support are required for those established on NIV (See Appendix 2). 926 • Supplementary oxygen may be required for long journeys. 927 928

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929 Venous thromboembolism (DVT and PE) 930 931 Prevention of VTE during air travel 932 The risk of VTE during air travel appears low overall and thromboprophylaxis is unnecessary for most 933 travellers. Prolonged travel in excess of 6 hours and/or the co-existence of another risk factor for VTE 934 increase the probability. The incidence of symptomatic VTE has been estimated to be 0.5% on flights 935 exceeding 12 hours, but asymptomatic rates may be higher (114, 115). The reasons for the increased 936 risk are unclear. Contributory factors may be prolonged immobility and dehydration, although these 937 are not conclusively proven. Other risk factors for VTE such as obesity, recent surgery, pregnancy, 938 malignancy and previous VTE all increase the overall risk for travel related VTE and may necessitate 939 additional prophylaxis. 940 941 General measures, including ambulation every 2-3 hours, ankle and calf exercises and avoidance of 942 alcohol or sedating drugs, should be recommended for most travellers. There is evidence that wearing 943 graduated compression stockings during travel reduces the incidence of deep venous thrombosis 944 (116). The data are sparse regarding the method or duration of pharmacological prophylaxis, and 945 recommendations rely on consensus expert opinion. Physicians may wish to recommend 946 pharmacological prophylaxis for those at higher risk of VTE, for example an obese patient planning a 947 flight exceeding 6 hours with a history of recent surgery. The risks of prophylaxis are thought to be 948 low. There is limited evidence for low molecular weight heparin (LMWH) as prophylaxis (117). The 949 use of Factor Xa inhibitors in this situation is off licence and currently has no evidence base. 950 951 Clinical Practice Points 952 • Avoid dehydration by drinking plenty of water. 953 • Avoid alcohol. 954 • Keep mobile if possible, by walking around or doing seat-based exercises once an hour 955 • Consider graduated compression stockings. 956 • LMWH or a DOAC are advised for both outward and return long haul flights (long haul defined 957 as flights of 6-12 hours) in high risk patients including those with a history of VTE; local policy 958 should be followed with regard to liaison with primary care and/or haematology services in 959 order to teach the patient how to administer the injection and dispose safely of the 960 equipment. 961 • All patients with a recent (< 6 weeks) history of VTE, especially any who presented with 962 significant right ventricular strain and decompensation should be reassessed before air travel.

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963 Air travel after VTE 964 Although the risks of prolonged air travel and development of VTE are well known, there are fewer 965 data on the risks associated with flying after a diagnosis of VTE. 966 967 A patient with a confirmed diagnosis of PE is highly likely to start anticoagulation, with the aim of 968 preventing the formation of new deep venous thrombi and further PEs. There is a general acceptance 969 that flying immediately after a diagnosis of pulmonary embolism/ DVT should be avoided. It appears 970 reasonable to assume that the sooner air travel occurs after a PE the greater the likelihood that 971 hypoxic pulmonary vasoconstriction will exacerbate ventilation-perfusion mismatch and raise 972 pulmonary pressures leading to an effect on cardiac output. 973 974 Some authors have suggested that most clot is resolved after 14-21 days, although there is variability 975 (118). Consensus opinion is to delay air travel if possible, usually for at least 2 weeks, although there 976 are no concrete data to support a safe time interval. Clot resolution depends principally on in vivo 977 fibrinolysis. Consideration should be given to the severity of the initial presentation. It is good 978 practice, before any proposed air travel, to reassess clinically a patient who has presented with 979 significant right ventricular strain and decompensation. 980 981 The probability of recurrent VTE while anticoagulated is very low. Recovered, stable patients who 982 remain on anticoagulation should be reassured accordingly, and advised to follow the above general 983 measures. 984 985 Clinical Practice Point 986 • Air travel should be delayed for two weeks after a diagnosis of DVT or pulmonary embolism. 987 988

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989 Pulmonary hypertension (PH) 990 The data are sparse in this area and recommendations are largely based on expert consensus opinion. 991 The concern in PH is the risk of hypoxia causing an increase in pulmonary arterial pressure and right 992 ventricular strain. Most studies addressing this issue have employed HCT. These have demonstrated 993 that most patients with PH can tolerate this degree of hypoxia with minor increases in dyspnoea (119). 994 Furthermore, the effect on the right ventricle in one study has been shown to be minimal (119). Most 995 of these studies have however only lasted for a short time (119), therefore prolonged exposure to 996 hypoxia as seen in long haul flights might be different. 997 998 One study has monitored patients during commercial flights (120). This showed that up to a quarter 999 of patients with PH desaturate during short haul flights, with higher altitude, ambulation and longer 1000 flights correlating with desaturations. Most tolerated this well, with fewer than 40% of participants 1001 reporting symptoms. A larger questionnaire based retrospective study has also confirmed that in most 1002 patients with stable PAH, flight is well tolerated with minimal clinical effects (121). Around half those 1003 surveyed travelled with supplementary oxygen. 1004 1005 Hypoxia reduces exercise capability; breathing oxygen-enriched air improves exercise capacity (119). 1006 It therefore appears logical to give patients with impaired functional capacity supplemental oxygen 1007 on board aircraft. Whether patients should have oxygen while ambulant as well as when resting is 1008 unknown; ambulatory oxygen on board presents obvious logistical challenges. 1009 1010 The 2011 BTS Recommendations advised that patients in New York Heart Association (NYHA) WHO 1011 functional class 3 or 4 should have supplemental oxygen during air travel (1). This recommendation 1012 is pragmatic rather than evidence based, and may result in over-prescribing of in-flight oxygen. One 1013 study suggests that more than double the number of patients would be recommended in-flight oxygen 1014 based on functional class rather than HCT outcome (119). Patients who already use long term oxygen 1015 at sea level are usually advised to double the flow rate. 1016 1017 Clinical practice points 1018 • Those in NYHA WHO functional class 3 or 4 are usually advised to have in-flight oxygen. If 1019 there is no evidence of hypercapnia to seem reasonable to suggest 2l/min by nasal cannulae. 1020 If there is evidence of hypercapnia HCT should be considered if available (122). 1021 • Those eligible for LTOT (sea level PaO2 < 8kPa at rest or air) should have in flight oxygen at 1022 double the flow rate recommended at sea level, provided there is no evidence of hypercapnia.

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1023 Lung cancer and mesothelioma 1024 When evaluating those with lung cancer or mesothelioma it is important to consider the nature and 1025 extent of their condition as well as their treatment. A pragmatic approach is to evaluate their risk of 1026 haemorrhage, pneumothorax, pleural effusion, VTE and any recent surgical and/or bronchoscopic 1027 interventions. 1028 1029 If taking medication, and particularly controlled drugs, patients must be aware of the appropriate 1030 documentation required for the countries they are visiting. Advance planning is essential. 1031 Clinical Practice Point 1032 • Patients who are undergoing chemotherapy should not travel while they are at increased risk 1033 of infection or suffering from significant side-effects, such as vomiting.

1034 Hyperventilation and dysfunctional breathing 1035 There are few data on the implications of functional breathing disorders for air travel, whether 1036 dysfunctional breathing (DB), vocal cord dysfunction (VCD) or inducible laryngeal obstruction (ILO). 1037 Many patients with dysfunctional breathing have asthma (123) and should be advised accordingly. 1038 1039 Acute shortness of breath is one of several symptoms for which flight diversion is advised (124). 1040 Diversions are costly, typically ranging from £10,000 - £80,000 depending on aircraft size and 1041 diversion destination (125). Dyspnoea caused by dysfunctional breathing or hyperventilation is 1042 unlikely to have serious clinical consequences, but must be distinguished from dyspnoea attributable 1043 to life-threatening acute medical conditions such as acute coronary syndrome or pulmonary embolism 1044 (1, 126). 1045 1046 Data from the last two decades suggest that 65% of in-flight medical emergencies were due to 1047 exacerbations of pre-existing conditions and that respiratory problems were most common; half were 1048 due to asthma or “asthma like” presentations (127-129). 1049 1050 Air travel can be stressful. Physiological or psychological stress may precipitate acute breathlessness 1051 in patients with respiratory disease (130). Acute hyperventilation can be a response to stress 1052 independently of lung pathology, usually in those with known panic and anxiety disorders(131). 1053 1054 Hyperventilation can cause bronchoconstriction resulting in “asthma like” symptoms (132) which are 1055 unresponsive to standard asthma medication (133, 134). A perception that the usual “rescue”

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1056 medication is “not working” may worsen an individual’s breathing pattern, causing concern to them, 1057 other passengers and air crew. Similar situations can arise with ILO or VCD, and onset of symptoms is 1058 often sudden (135). 1059 1060 Where DB is linked to respiratory conditions, particularly asthma, national and international guidelines 1061 endorse breathing exercise programmes provided by a specialist respiratory physiotherapist as an 1062 adjuvant to pharmacological treatment. Patients should be advised to use breathing techniques in 1063 situations where breathlessness may become problematic (65, 136). ILO and VCD, which can present 1064 with acute respiratory distress and stridor, may be treated with breathing exercises taught by a 1065 respiratory physiotherapist or speech therapist specializing in paradoxical vocal fold movement (137). 1066 1067 Paper bag rebreathing is no longer recommended, because inspired oxygen concentration decreases 1068 sufficiently to endanger hypoxic patients. There are data reinforcing that significant harm to patients 1069 can result from acute myocardial infarction, pneumothorax and pulmonary embolism being 1070 misdiagnosed as hyperventilation (138) (139). 1071 1072 Clinical Practice Points

1073 • Patients with DB, ILO and/or VCD should be referred to specialist Respiratory Physiotherapy 1074 for advice on symptom management before travel. 1075 • Those with anxiety disorders should be reviewed before travel, including their medication 1076 compliance, and use of short acting anxiolytics encouraged. 1077 • Other life-threatening conditions presenting with dyspnea should be excluded on board as far 1078 as possible. 1079 • Supplemental oxygen should be given on board if the cause of dsypnoea is unclear. 1080 • Rebreathing via a paper bag is not recommended.

1081

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1082 Acknowledgements 1083 To be completed

1084 Disclaimer 1085 A Clinical Statement reflects the expert views of a group of specialists who are well versed on the topic 1086 concerned, and who carefully examine the available evidence in relation to their own clinical practice. 1087 A Clinical Statement does not involve a formal evidence review and is not developed in accordance 1088 with clinical practice guideline methodology. Clinical Statements are not intended as legal documents 1089 or a primary source of detailed technical information. Readers are encouraged to consider the 1090 information presented and reach their own conclusions. 1091 1092 Declarations of interest 1093 Declarations of interest were completed in line with the BTS Policy and are available from the BTS 1094 Office on request. 1095

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1096 Appendix 1 1097 Practical considerations

1098 Exertion

1099 Passengers should keep active by undertaking seat-based exercises and/or standing at intervals if 1100 flight conditions permit.

1101 It therefore seems prudent to recommend that passengers with significant respiratory limitation, 1102 regardless of whether travelling with in-flight oxygen, should request an aisle seat near a toilet to 1103 avoid long periods of walking

1104 Patients who cannot tolerate being without supplemental oxygen for even a short period of time 1105 should not travel by air, as there will be times when oxygen cannot be supplied 1106 Oxygen should be considered for those staying at high altitude destinations. 1107 1108 Useful websites 1109 1110 Aerospace Medical Association www.asma.org 1111 British Lung Foundation www.blf.org.uk 1112 British Thoracic Society www.brit-thoracic.org.uk 1113 Centers for Disease Control wwwnc.cdc.gov/travel 1114 Civil Aviation Authority www.caa.co.uk/Passengers 1115 Cystic Fibrosis Worldwide www.cfww.org 1116 European Lung Foundation www.europeanlung.org 1117 European Federation of Allergy and Airways Diseases Patients’ Associations www.efanet.org 1118 International Air Transport Association www.iata.org 1119 International Civil Aviation Organisation www.icao.int 1120 International Society of Travel Medicine www.istm.org 1121 For alternatives to air travel please refer to www.seapuffers.com 1122 Advice for passengers travelling with HIV: 1123 The Terrence Higgins Trust: 1124 www.tht.org.uk/hiv-and-sexual-health/living-well-hiv/your-rights/travelling-hiv 1125 Advice for passengers travelling with a heart condition: 1126 The British Heart Foundation: 1127 www.bhf.org.uk/informationsupport/support/practical-support/holidays-and-travel 1128

1129

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1130 Appendix 2 1131 Logistic of air travel with equipment 1132 1133 As noted previously, not all portable concentrators work as intended when taken to altitude, rather 1134 than pulse-dose oxygen itself which works fine when provided by a cylinder and conserving device 1135 (140). 1136 1137 Pulse-dose oxygen may not be suitable for patients with a fast and shallow respiratory pattern or for 1138 use during sleep (141, 142), and it is also worth noting that pulse-dose settings do not equate to the 1139 equivalent continuous flow rates (64), and that not every POC functions well when taken to altitude 1140 (140). One author found significantly lower PaO2 values when using a POC when compared to 1141 compressed oxygen with a conserving device, while stating that acceptable inflight values are 1142 achievable with portable oxygen concentrators although the dose may need to be increased (49). 1143 Wherever possible, assessment should take place using the same equipment as that which will be 1144 used on board the aircraft. 1145 1146 Some POCs are limited to pulse-dose only, and this may not be suitable (64). Currently available POCs 1147 that do supply continuous flow oxygen cannot provide flow rates above 3 L/min. Please refer to 1148 POC documentation to check that the equipment meets the passenger's requirements before 1149 prescribing/hiring for air travel. 1150 1151 Travel with CPAP 1152 Few airlines, if any, will allow any medical device to be powered via the aircraft power supply, 1153 therefore an appropriate battery must be used. The device and battery specifications must be 1154 approved for use by the airline before travel. Battery performance should be checked by the user 1155 beforehand, so there is an understanding of operating times on their usual settings. 1156 1157 Further consideration needs to be given to CPAP use during flight and at high altitude destinations as 1158 it requires a machine that will perform adequately at low ambient pressure. The 2011 BTS guidance 1159 (1) reported that a fixed-pressure CPAP machine without pressure compensation set to deliver a 1160 pressure of 12 cm H2O at sea level may deliver only 9 cm H2O at 8000 ft, and may therefore require 1161 adjustment to ensure a safe level of treatment throughout the flight. If continuous flow oxygen cannot 1162 be provided by the airline or by POC, oxygen and CPAP cannot be used simultaneously. The availability 1163 of distilled water for humidifiers may be restricted. 1164

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1165 Patients on NIV 1166 For patients established on NIV, further planning and advice are required to support the use of NIV 1167 during flight. If continuous flow oxygen cannot be provided by the airline or by POC, oxygen and NIV 1168 cannot be used simultaneously. A decision around whether NIV or supplementary oxygen is of 1169 greatest physiological importance to the patient is then required on an individual basis. The previous 1170 travel history, current clinical condition and the presence or absence of overnight travel should also 1171 be considered. 1172 1173

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1174 Appendix 3: Quick reference guide for Respiratory Physiologists 1175 1176 HCT Methods 1177 The HCT uses an inspired gas mixture containing 15% oxygen, which gives an approximate similar

1178 inspired oxygen tension (PO2) to breathing air at the maximum allowable cabin pressure altitude 1179 (2,438m, or 8,000ft)(46, 47). HCT is usually performed in a specialist respiratory physiology unit. The 1180 provision of a 15% oxygen gas mixture can be achieved as follows: 1181 1182 • A pre-mixed cylinder containing a 15% oxygen gas mixture can be obtained from medical gas 1183 providers, or Douglas bags can be mixed with air and nitrogen to reduce the percentage of 1184 inspired oxygen to 15%, both to supply a tight-fitting face mask in a closed circuit [5] 1185 • Pure nitrogen can be introduced into a sealed chamber such as a body plethysmograph for 1186 paediatric or mask-intolerant patients, removing the need for a face mask [13]. Paediatric 1187 patients can be sat in a body plethysmograph on an adult’s lap throughout [5]; the adult

1188 should also undergo SpO2 monitoring to avoid excessive hypoxaemia. A body box is generally 1189 used for children, although some paediatric laboratories use masks. 1190 • A 40% Venturi oxygen mask can be used with pure nitrogen as the driving gas, giving a 1191 resultant gas mixture containing approximately 15% oxygen [6, 14] 1192 • A hypoxic gas generator, similar to an oxygen concentrator, can be used to provide a 1193 continuous supply of variable hypoxic gas mixtures to supply a mask or closed chamber, which 1194 can be the most cost-effective method for centres with a high demand for HCT [15] 1195

1196 The patient usually breathes the hypoxic gas mixture for 20 minutes, or until SpO2 reaches 85%. 1197 Although this is shorter than the briefest commercial flight, oxygenation equilibrium is usually reached

1198 within this time (119, 143). The patient is advised to have in-flight oxygen if PaO2 falls below 6.6 kPa

1199 (<50 mm Hg) or SpO2 remains <85% (28, 30) (see page 11). 1200 1201 HCT with oxygen

1202 If PaO2 or SpO2 values meet the criteria, in-flight oxygen is recommended (30). The flow rate required 1203 can be assessed as part of the HCT (28). Previous BTS recommendations advised in-flight oxygen to 1204 be supplied at 2 or 4 l/min via nasal cannulae, which were for many years the only fixed flow rates 1205 routinely available on commercial aircraft. As airline-supplied in-flight oxygen becomes less common 1206 and greater numbers of patients travel with flight-approved portable oxygen concentrators (POCs)

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1207 delivering a wide range of continuous and intermittent flow rates, these figures are less critical. The 1208 HCT should ideally be performed with the modality that is intended for use in-flight. 1209 1210 Pulse-dose delivery is not suitable for young children, for use during sleep (13, 51) or for certain adults. 1211 Not all portable concentrators function as expected under conditions of simulated altitude (140) and 1212 pulse-dose settings may not equate to equivalent continuous flow rates (see Appendix 2). 1213 1214 Patients with hypercapnia 1215 Previous BTS advice was to err on the side of recommending oxygen if in doubt (1), and other authors 1216 have recommended doubling oxygen flow rates for patients with a pre-existing oxygen requirement 1217 (1, 23). However, there is a potential risk of developing hypercapnia and respiratory acidosis from 1218 oxygen during HCT in patients with type 2 respiratory failure (14). Patients with a history of 1219 hypercapnia should ideally undergo HCT with blood gas sampling. In these cases the minimum

1220 amount of oxygen should be delivered to maintain PaO2 ≥6.6 kPa while monitoring PaCO2 and pH. If

1221 blood gas sampling is not available then care should be taken not to raise SpO2 above the resting level 1222 with supplementary oxygen in this group of patients(28) [13]. In some cases it may be unsafe to

1223 undertake air travel even if good oxygenation can be achieved, if adverse PCO2 and pH changes are 1224 evident (14). 1225 Table 1 Hypoxic challenge test (HCT) outcomes and Clinical Practice Points HCT outcome Clinical Practice Points

PaO2 ≥ 6.6 kPa (≥ 50 mm Hg); In-flight oxygen not required SpO2 ≥ 85% PaO2 < 6.6 kPa (<50 mm Hg); Repeat HCT with oxygen (flow rate and modality ideally the same SpO2 <85% as that to be given on board aircraft): • Titrate oxygen to maintain PaO2 ≥ 6.6 kPa or SpO2 ≥ 85% • Monitor pH and pCO2 if there is a history of hypercapnia • Consider advising against air travel if pH falls to <7.35 and PCO2 increases by > 1 kPa (7.5 mm Hg) from baseline when PaO2 is maintained at ≥ 6.6 kPa or SpO2 ≥85%

1226 1227 Note: 1228 The use of arterial or capillary blood gas sampling is preferred if available. Blood gases are not routinely measured in children. 1229 Recommendations on pCO2 & pH changes are based on the 2015 BTS guideline for home oxygen use in adults (15). 1230

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