Descriptors of Dyspnea in Obstructive Lung Diseases Descrittori Di Dispnea Nelle Patologie Ostruttive Delle Vie Aeree

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Multidisciplinary Focus on: Dyspnea edited by / a cura di Giorgio Scano Descriptors of dyspnea in obstructive lung diseases Descrittori di dispnea nelle patologie ostruttive delle vie aeree

Sabina A. Antoniu University of Medicine and Pharmacy “Gr. T. Popa” Iasi, Department of Internal Medicine II - Pulmonary Disease, Pulmonary Disease University Hospital

ABSTRACT descrittori) con i meccanismi fisiologici e fisiopatologici sot- In obstructive lung diseases such as asthma and COPD dysp- tostanti. Questi studi sono stati effettuati nell’asma piutto- nea is a common respiratory symptom with different charac- sto che nella BPCO ed i descrittori di dispnea sono stati ri- teristics given the different pathogenic mechanisms: in COPD scontrati utili per identificare i pazienti con asma in pericolo initially it can occur during exertion but then it increases pro- di vita. Tuttavia studi ulteriori sono necessari per esplorare ul- gressively along with the airflow obstruction, whereas in teriormente questi descrittori e la loro utilità clinica. In que- asthma it occurs episodically and is caused by transient bron- sta rassegna vengono analizzati i meccanismi della dispnea choconstriction. nei vari sottogruppi di patologie respiratorie di tipo ostrutti- The language of dyspnea includes a large range of clinical vo, come pure i descrittori di dispnea e la loro utilità nella pra- descriptors which have been evaluated for their correlation (of tica clinica. one or several descriptors) with underlying physiologic/phys- iopathologic mechanisms. These studies were done in asthma Parole chiave: Descrittori, dispnea, patologie ostruttive respi- rather than in COPD, and dyspnea descriptors were found to be ratorie, test da sforzo. useful in identifying patients with life-threatening asthma. However further studies are needed to further explore such descriptors and their clinical utility. INTRODUCTION This review discusses dyspnea mechanisms in various Obstructive lung diseases are represented mainly by obstructive lung disease subsets as well as the descriptors of dyspnea and their utility in clinical practice. asthma and by chronic obstructive pulmonary disease (COPD) which are both inflammatory diseases Keywords: Descriptors, dyspnea, exercise testing, obstructive lung of the airways but with different pathogenesis and diseases. clinical manifestations: in asthma inflammation is triggered and maintained usually by allergens, ren- RIASSUNTO ders the bronchial muscle hyperreactive to various Nelle patologie ostruttive respiratorie come l’asma e la BPCO stimuli including allergens themselves, and the con- la dispnea è un sintomo molto comune, con caratteristiche sequent bronchospasms manifest clinically with differenti a seconda del meccanismo patogenetico sotteso: episodic dyspnea and wheezing subsequently nella BPCO si verifica inizialmente durante esercizio fisico per relieved with rescue bronchodilator medication. In poi incrementare progressivamente col progredire dell’ostru- zione bronchiale, mentre nell’asma insorge episodicamente COPD cigarette smoking exposure is the main risk ed è causata da un broncospasmo transitorio. factor and the airways inflammation resulting from Il linguaggio della dispnea include un’ampia varietà di descrit- such aggression is progressive, reducing the airways tori clinici di cui è stata valutata la correlazione (di uno o più lumen, and respiratory symptoms are dominated by

+ Sabina A. Antoniu University of Medicine and Pharmacy “Gr.T.Popa” Iasi, Department of Internal Medicine II- Pulmonary Disease, Pulmonary Disease University Hospital 30 Dr I Cihac Str, 700115 Iasi, Romania email: [email protected] Data di arrivo: 09/04/2010 – Accettato per la pubblicazione: 20/04/2010 Multidisciplinary Respiratory Medicine 2010; 5(3): 216-219

216 MRM Descriptors of dyspnea – SA Antoniu dyspnea, cough and sputum production which are augmented by increased ventilatory demands increase in severity with disease progression or dur- due to ventilation perfusion mismatches, metabolic ing disease exacerbations. acidosis, hypoxemia, increased sympathetic tone, Dyspnea is a common clinical denominator in both etc. [1]. asthma and COPD and its different characteristics Gas exchange abnormalities occurring in COPD in the two diseases reflect the different pattern of patients during exercise are represented by arterial inflammation and of airways obstruction. This hypoxemia and/or hypercapnia: the former occurs review discusses separately the mechanisms of dys- in the milder COPD stages due to reduced ventila- pnea in asthma and COPD, its descriptors, and their tion and shunting, whereas in more advanced clinical utility. COPD alveolar hypoventilation adds to the above Descrittori di dispnea mentioned mechanisms. Exercise hypercapnia in COPD is due to reduced respiratory drive, breath- DYSPNEA IN COPD ing patterns altered to minimize respiratory discom- In COPD dyspnea is one of the main respiratory fort, or ventilatory muscle fatigue and has been symptoms present during stable or exacerbated shown to be associated with greater dynamic hyper- state. It manifests initially during exertion and then, inflation [3]. as the disease progresses, also during rest. It is Neuromechanical dissociation (NMD) between the caused by airflow obstruction which is secondary to attempted and actual respiratory effort which airways inflammation, airways remodelling and occurs between efferent motor neurons and afferent sputum hypersecretion; reduced lung elastic recoil fibers has been hypothesised as a physiopathogenic due to emphysema and the obstruction of small air- mechanism in chronic obstructive pulmonary dis- ways result in incomplete air expelling and dynam- eases such as COPD and asthma [1]. In a study ic hyperinflation (“air trapping”) [1]. evaluating the perception of exertional breathlessness during symptom-limited incremental cycle Mechanisms of dyspnea in COPD exercise testing in normal subjects and in patients Overall exertional dyspnea in COPD is the result of with chronic airflow limitation, perceived inspirato- complex pathohysiological mechanisms including ry difficulty was assessed with the Borg scale dynamic hyperinflation, increased ventilatory (BorgIN), inspiratory effort was evaluated with demand relative to impaired capacity, hypoxemia, esophageal pressure expressed as a fraction of max- hypercapnia, and neuromechanical dissociation imal esophageal pressure at isovolume (Table I) [1]. [Pes/PImax]), and breathing pattern, operational During exercise the reduced pulmonary elastic lung volumes (end-expiratory/inspiratory lung vol- recoil contributes to an increase in the end-expira- umes [EELV/EILV]) were measured and compared at tory lung volume, and dynamic hyperinflation (DH) a standard V˙O2 of 50% predicted maximum. occurs. There are several adaptive mechanisms to Breathlessness descriptors chosen and reported the DH, including the reconfiguration of the rib immediately after exercise differed between normal cage in order to contain the overinflated lungs, and subjects and patients with chronic airflow obstruc- an increased activity of the respiratory muscles, in tion. Descriptors of increased ‘work/effort’ and particular of the diaphragm, in order to generate ‘heaviness’ of breathing were chosen by both nor- increased pressures able to compensate the mal subjects and patients with airflow obstruction reduced elastic recoil, but such mechanisms can whereas the latter category constantly chose usually be compensatory during resting or during descriptors such as ‘increased inspiratory difficulty’ more reduced airways inflammation (such as in sta- (75%), ‘unsatisfied inspiratory effort’ (75%), and ble disease). During exertion or increased inflam- ‘shallow breathing’ (50%). The ratio of Pes/PImax to mation (exacerbation) the increased DH impairs the VT/predicted VC was identified as the strongest cor- ability of the respiratory muscles to increase the relate with the Borg scale [4]. intrathoracic pressure in response to the increased The differences between the quality of descriptors drive of breathing. The increased breathing rate is for dyspnea among healthy subjects and patients consequent to the inability of the overinflated lung with airflow obstruction suggest that the latter cate- to maintain or increase the inspiratory capacity dur- gory receives altered peripheral sensory afferent ing exercise [2]. During exercise such abnormalities information from mechanoreceptors in the respiratory muscles, chest wall and lungs signaling to them that the mechanical response of the ventilatory sys- tem is insufficient or inappropriate for the effort expended [5]. TABLE I: PATHOPHYSIOLOGICAL MECHANISMS OF DYSPNEA This sense of increased effort is believed to be the IN COPD result of corollary discharge relayed from the motor cortex to the sensory cortex in the forebrain. Unlike • Dynamic lung hyperinflation normal subjects, in whom respiratory effort matches • Increased ventilatory demand relative to impaired capacity the ventilator demand both at rest and during exer- • Hypoxemia cise, in patients with COPD there is increasing dis- • Hypercapnia parity between effort and ventilatory output (i.e. • Neuromechanical dissociation neuromechanical dissociation) which becomes

MRM 217 more prominent as exercise progresses, because TABLE II: FACTORS AFFECTING SYMPTOMS PERCEPTION IN dynamic hyperinflation constrains tidal volume ASTHMA expansion. Consequently COPD patients experi- ence intolerable dyspnea very quickly during exer- • Advanced age cise, and describe it as ‘no room to breathe’ [5]. • Suboptimal disease therapeutic control (presence of airways hyperreactivity, peak expiratory flow variability) • Chronic airflow obstruction DYSPNEA IN ASTHMA • Asthma medications In asthma dyspnea is the clinical manifestation of • Personality/psychological traits episodic bronchospasm, and its presence represents a sign of suboptimal (therapeutic) control of the dis- From [2], mod. ease. Its severity can vary with the severity of the asthma attack or exacerbation and it can be perceived differently. For instance, some patients can perceive promptly the mild respiratory symptoms with increasing frequency, i.e. an asthma exacerba- 50% from baseline in asthma) in which the qualita- tion occurring while on maintenance therapy, and tive descriptors of dyspnea and functional residual can act promptly by self administering appropriate capacity (FRC) were measured at the doses nearest medication in order to reduce the flared inflamma- to the provocative concentration of methacholine tion; other patients, on the contrary, are unable to causing a 20% fall in FEV1(PC20) and at the highest perceive appropriately such symptoms at their onset dose of methacholine (maximum response), asthma Multidisciplinary Respiratory Medicine 2010; 5(3): 216-219 5(3): Medicine 2010; Multidisciplinary Respiratory and may seek medical care for a severe/life-threat- patients selected descriptors such as ‘inspiratory dif- ening asthma. ficulty’, ‘chest tightness’, ‘unsatisfied inspiration’, or Dyspnea perception in asthma can be influenced ‘work’ at the dose nearest to PC20 but were more by various factors (Table II) and knowledge of these frequently selected at the highest methacholine factors as well as of the descriptors of dyspnea may dose. Furthermore patients who reported chest contribute to improve disease control. tightness at maximum response had greater airflow obstruction and dynamic hyperinflation than those Dyspnea perception and its influencing factors in who did not report chest tightness [10]. asthma Under therapy, the frequency of reporting descrip- In asthma it is difficult to differentiate between ‘nor- tors such as ‘chest tightness’ has been found to mal’ and ‘abnormal’ (poor or exaggerated) percep- decrease, whereas the frequency of reporting others tion of dyspnea [2]. Poor perception of dyspnea such as ‘work’ or ‘breathing effort’ persisted con- means underestimation of its severity and this has comitantly with airflow obstruction [11,12]. been demonstrated to be a major risk factor for life- threatening asthma (LTA) and disease CONCLUSIONS morbidity/mortality: in a study evaluating symptoms perception in subjects undergoing methacoline The clinical descriptors of dyspnea in asthma and bronchoprovocation testing, about 15% of the 82 COPD can be relevant for both diagnostic and ther- patients with a fall of FEV1 to values < 50% predict- apeutic purposes: in the initial clinical evaluation of ed were reported to be asymptomatic, whereas in an unexplained dyspnea they might be able to pro- another study in patients with history of near fatal vide information which is additional to the evalua- asthma perception of dyspnea during external resis- tion of physiologic parameters, e.g. in a patient with tive loading was found to be lower compared to COPD asymptomatic at rest, obtaining descriptors normal subjects but comparable to that of patients for exertional dyspnea factors can help in identify- with non fatal asthma, and low perception of dysp- ing the limiting factor of the exercise capacity, or in nea was found to be associated with significantly a patient with asthma certain dyspnea descriptors longer hospitalisations, near fatal exacerbations can signal suboptimal therapeutic control of disease and/or death [6-8]. or may help in detecting life threatening forms of In asthma, dyspnea is usually described as ‘chest asthma. tightness’, increased ‘effort’ or ‘work’ of breathing, The language of dyspnea includes a large range of or ‘difficult breathing’, and it has been demonstrat- descriptors, and although a certain amount of ed that the symptom quality varies with the degree research evaluating the correlation of one or several of bronchoconstriction, e.g. the tightness was found descriptors with underlying physiologic/pathophys- to be associated with mild bronchoconstriction and iologic mechanisms has been already done, more attributed to vagal stimulation due to increased air- studies are needed to further explore such descrip- ways resistance but not to dynamic hyperinflation tors and their clinical utility. [9]. Such studies can be greatly helped by the use of However, in a study evaluating the relationship dyspnea questionnaires which offer standardized between respiratory symptom intensity and quality clinical descriptors able to detect rapidly the cause and dynamic lung hyperinflation during bron- of breathing abnormalities: despite the fact such choconstriction induced by high-dose metha- questionnaires are commonly used in COPD to choline challenge (maximum decrease in FEV1 of evaluate dyspnea and the effects of various thera-

218 MRM Descriptors of dyspnea – SA Antoniu pies on its severity, few studies have focused on dys- interest, a clinical applicability in disease diagnosis, pnea descriptors and their clinical utility in COPD; in severity ascertainment and in therapeutic follow this has more frequently been done in asthma and up, and further studies can therefore improve the the results obtained and discussed above should knowledge in the field. encourage similar studies in COPD. CONFLICT OF INTEREST STATEMENT: The author has no con- Overall documentation of dyspnea descriptors in flict of interest to declare in relation to the subject of this man- obstructive lung diseases has, beyond pure research uscript. Descrittori di dispnea

References

1. O'Donnell DE, Webb KA. Mechanisms of dyspnea in K, Takishima T. Chemosensitivity and perception of dyspnea COPD. In: Mahler D, O'Donnell DE, eds. Dyspnea, mech- in patients with a history of near-fatal asthma. N Engl J Med anisms, measurement and management. Boca Raton, FL, 1994;330:1329-1334. Taylor and Francis Group 2005:29-58. 8. Magadle R, Berar-Yanay N, Weiner P. The risk of hospitaliza- 2. Lougheed MD, O'Donnell DE. Dyspnea in asthma. In: tion and near-fatal and fatal asthma in relation to the per- Mahler D, O'Donnell DE, eds. Dyspnea, mechanisms, ception of dyspnea. Chest 2002;121:329-333. measurement and management. Boca Raton, FL, Taylor and 9. Simon PM, Schwartzstein RM, Weiss JW, Fencl V, Francis Group,2005:59-86. Teghtsoonian M, Weinberger SE. Distinguishable types of 3. Boulet LP, Leblanc P, Turcotte H. Perception scoring of dyspnea in patients with shortness of breath. Am Rev Respir induced bronchoconstriction as an index of awareness of Dis 1990;142:1009-1014. asthma symptoms. Chest 1994;105:1430-1433. 10 Lougheed MD, Fisher T, O'Donnell DE. Dynamic hyperin- 4. O'Donnell DE, Bertley JC, Chau LK, Webb KA. Qualitative flation during bronchoconstriction in asthma: implications aspects of exertional breathlessness in chronic airflow limitation: pathophysiologic mechanisms. Am J Respir Crit Care for symptom perception. Chest 2006;130:1072-1081. Med 1997;155:109-115. 11. Manning HL, Schwartzstein RM. Respiratory sensations in 5. O'Donnell DE. Hyperinflation, dyspnea, and exercise intol- asthma: physiological and clinical implications. J Asthma erance in chronic obstructive pulmonary disease. Proc Am 2001;38:447-460. Thorac Soc 2006;3:180-184. 12. Moy ML, Lantin ML, Harver A, Schwartzstein RM. Language 6. Rubinfeld AR, Pain MC. Perception of asthma. Lancet of dyspnea in assessment of patients with acute asthma 1976;1:882-884. treated with nebulized albuterol. Am J Respir Crit Care Med 7. Kikuchi Y, Okabe S, Tamura G, Hida W, Homma M, Shirato 1998;158:749-753.

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