Bronchoconstriction in Response to Deep Inhalation During Spirometry Testing Jeffrey M Haynes RRT RPFT Introduction 12°F. According to the patient, a therapeutic trial of albu- terol via metered-dose inhaler ameliorated both symptom In healthy individuals, airway resistance has an inverse frequency and severity. An additional asthma risk factor relationship with lung volume.1 Moreover, deep inhalation was significant atopy with sensitivities to cats, dogs, horses, is thought to maintain airway smooth muscle homeostasis pollen, trees, and grass. and to possess bronchodilating and bronchoprotective prop- On the day of testing, pulmonary function instrumenta- erties against challenge agents.2-6 The bronchodilatory ef- tion passed calibration verifications, and there had been no fect of deep inhalation is clearly impaired in asthma pa- recent issues with instrument functionality or biologic con- tients2,7,8; however, the bronchoprotective properties of trol testing. The patient demonstrated excellent spirometry deep inhalation against challenge test agonists (eg, meth- technique without evidence of submaximal lung inflation acholine) remain robust in many asthma patients with mild before forced exhalation; however, a progressive decline 5,6 11 airway hyper-responsiveness. In some asthma patients, in the FVC and FEV1 was observed (Table 1). The pa- however, deep inhalation can produce paradoxical bron- tient developed some coughing and reported mild chest choconstriction.5,9,10 This case describes a patient who de- tightness. In addition to the progressive decline in numer- veloped significant bronchoconstriction in response to deep ical values and accompanying symptoms, the emergence inhalation during spirometry testing. of more concave expiratory flow-volume loops further strengthened the suspicion of paradoxical bronchoconstric- Case Summary tion in response to the deep inhalation required in spirom- etry testing. The flow-volume loops from efforts 1 and 6 are superimposed in Figure 1. All spirometry efforts sat- A 49-y-old white male presented to the pulmonary func- isfied American Thoracic Society/European Respiratory tion laboratory for spirometry, specific airway conduc- Society acceptability criteria; however, repeatability crite- tance (sG ), lung volume testing, and methacholine chal- aw ria were not satisfied as an apparent consequence of pro- lenge. The patient had smoked one package of cigarettes/d gressive bronchoconstriction.12 for 20 y until he quit 1 y before testing. He reported a Typically, the largest FVC and FEV should be reported history of childhood asthma, which had been quiescent 1 as the best-effort values12; however, in this case, it was throughout his adult life. However, in recent months, the decided that the largest of the last 3 efforts (effort 6; see patient reported increasing wheezing and chest tightness after exercise. He noted that symptomatic episodes seemed Table 1) should be reported as the best effort. The data to occur more frequently following outdoor exercise in from all efforts and the technologist’s suspicion of deep cold air. The local temperature on the day of testing was inhalation-induced bronchoconstriction were shared with the interpreting physician. The rationale for this decision was as follows: Paradoxical bronchoconstriction from deep inhalation was suspected, and the yet-to-be-performed lung Mr Haynes is affiliated with the Pulmonary Function Laboratory, St volumes and sGaw testing should be linked to data repre- Joseph Hospital, Nashua, New Hampshire. sentative of the current state of ventilation. The state of Mr Haynes has disclosed no conflicts of interest. ventilation that accompanied effort 1 no longer existed, and coupling lung volume and sGaw data to a then-non- Correspondence: Jeffrey M Haynes RRT RPFT, Pulmonary Function existent milieu might be misleading and potentially affect Laboratory, St Joseph Hospital, 172 Kinsley Street, Nashua, NH 03060. test interpretation. The reported baseline spirometry, lung E-mail: [email protected]. volume, and sGaw data via whole-body plethysmography DOI: 10.4187/respcare.03995 are listed in Table 2. Lung volume data indicated signifi- RESPIRATORY CARE • MAY 2015 VOL 60 NO 5 e105 BRONCHOCONSTRICTION DURING SPIROMETRY TESTING Table 1. Serial FVC and FEV1 Measurements During Baseline Spirometry Testing Effort FVC (L) % Predicted* Z Score* Change (%) FEV1 (L) % Predicted* Z Score* Change (%) 1 5.05 92 Ϫ0.61 NA 3.28 76 Ϫ1.84 NA 2 4.98 91 Ϫ0.71 Ϫ1 3.09 72 Ϫ2.18 Ϫ6 3 4.60 84 Ϫ1.23 Ϫ9 2.85 66 Ϫ2.61 Ϫ13 4 4.49 82 Ϫ1.38 Ϫ11 2.63 61 Ϫ3.01 Ϫ20 5 4.42 80 Ϫ1.47 Ϫ12 2.62 61 Ϫ3.02 Ϫ20 6 4.60 84 Ϫ1.23 Ϫ9 2.74 64 Ϫ2.81 Ϫ16 7 4.36 79 Ϫ1.56 Ϫ14 2.54 60 Ϫ3.08 Ϫ22 * Based on reference equations by Quanjer et al.11 NA ϭ not applicable Fig. 1. Superimposed flow-volume loops and volume-time curves from spirometry effort 1 (indicated by arrow) and effort 6. Effort 6 shows lower flows and volumes compared with effort 1. cant air-trapping with a residual-volume-to-total-lung- ing bronchodilator administration would have been re- capacity ratio of 41%. In addition, the sGaw was below the ported. lower limit of the normal range. Because of baseline obstruction, the methacholine chal- Discussion lenge test was cancelled per laboratory protocol, and bron- chodilators (2.5 mg of albuterol and 0.5 mg of ipratropium Spirometric indices are measured to assess lung me- via small-volume nebulizers) were administered. The chanics and structure via inverse modeling (ie, predict patient demonstrated a significant response to bronchodi- structure from function).13 Individuals who perform and lators with complete reversal of air-trapping and normal- interpret spirometry tests need to be aware that the deep ization of the FVC, FEV1, and sGaw (see Table 2). The inhalation required in the test can affect the existing func- pre-bronchodilator and post-bronchodilator flow-volume tional state both positively and negatively. Deep inhalation loops are superimposed in Figure 2. It is noteworthy that during spirometry testing has the potential to dilate or even if the highest FEV1 value (3.28 L, effort 1) had been constrict the airways and protect against bronchial chal- 2-10 chosen as the best effort, a 24% increase in FEV1 follow- lenge agents (eg, methacholine). A lack of appreciation e106 RESPIRATORY CARE • MAY 2015 VOL 60 NO 5 BRONCHOCONSTRICTION DURING SPIROMETRY TESTING Table 2. Pulmonary Function Data Pre-Bronchodilator and Post-Bronchodilator Pre-Bronchodilator Post-Bronchodilator Lower Limit of Actual % Predicted Z Score Actual % Predicted Z Score Change (%) the Normal Range FVC (L) 4.60 4.3 84 Ϫ1.2 5.85 106 0.48 ϩ27 Ϫ Ϫ ϩ FEV1 (L) 2.74 3.4 64 2.8 4.06 94 0.45 48 Ϫ Ϫ ϩ FEV1/FVC 0.60 0.7 NR 3.15 0.69 NR 1.66 15 TLC (L) 7.81 6.6 101 NR 7.60 99 NR Ϫ3 RV (L) 3.21 3.0* 141 NR 1.72 76 NR Ϫ46 RV/TLC 0.41 0.4* 124 NR 0.23 70 NR Ϫ44 ͓ ͔ ϩ sGaw ( (L/s)/cm H2O /L) 0.05 0.1 NR NR 0.15 NR NR 200 * Upper limit of the normal range. TLC ϭ total lung capacity RV ϭ residual volume sGaw ϭ specific airway conductance NR ϭ not reported Fig. 2. Pre-bronchodilator and post-bronchodilator flow-volume loops and volume-time curves. for the potential effects of deep inhalation during spirom- spirometry. Historically, this phenomenon has been attrib- etry testing may lead to incorrect conclusions regarding uted to deep inhalation and not the expiratory phase of the the functionality of instruments and the quality of patient maneuver. Moore et al14 showed no difference in response test performance. Moreover, the use of a dosimeter meth- to methacholine between challenge tests that incorporated acholine challenge test protocol that encourages inhalation repeated exhalation to residual volume (without deep in- to total lung capacity can result in false-negative challenge halation) and those that prohibited both deep inhalation tests.5,6 The obvious danger of any false-negative diagnos- and forced exhalation. In contrast, Suzuki et al15 showed a tic test is misdiagnosis and a misguided treatment plan. decline in sGaw following an expiratory maneuver from In this case, an asthma patient (as determined by post- functional residual capacity; however, the decline associ- test probability) exhibited bronchoconstriction as a conse- ated with expiration was smaller than the decline associ- quence of the deep inhalation necessary to perform forced ated with deep inhalation. RESPIRATORY CARE • MAY 2015 VOL 60 NO 5 e107 BRONCHOCONSTRICTION DURING SPIROMETRY TESTING ory, they measured sGaw in subjects with asthma and without asthma after deep inhalation with and without a resistive element in situ. Only the subjects with asthma demonstrated significant decreases in sGaw after deep in- halation with added resistance. Lim et al10 suggested that repeated deep inhalation has the potential to worsen air- flow obstruction as a consequence of reduced deflation recoil. These data should prompt clinicians to exercise caution when asking acutely ill asthma patients to repeat- edly perform deep inhalation for spirometry testing, peak- flow measurements, and auscultation. Teaching Points • Deep inhalation have the potential to cause bronchoc- onstriction during spirometry testing. • Careful observations are necessary to distinguish this phenomenon from instrument malfunction and subopti- mal patient effort and technique. • When bronchoconstriction is observed during spirome- Fig. 3. Magnetic resonance ventilation images after inhalation of try testing, reporting the highest values as the best val- hyperpolarized helium. A: Normal volunteer with homogeneous distribution of ventilation. B: Mild asthma. C: Moderate asthma. D: ues may be misleading, especially when these values are Severe asthma. Arrows indicate ventilation defects. (From Refer- linked to tests that are performed after the bronchocon- ence 16, with permission.) striction has occurred.