An example of ventilatory limitation during cardiopulmonary exercise testing in a patient with COPD.

A 64-year-old obese gentleman attended for further evaluation of ongoing dyspnoea in the context of a previous diagnosis of moderate COPD treated with dual long-acting bronchodilators. A cardiopulmonary exercise test (CPET) was performed, which demonstrated reduced peak work and oxygen consumption with evidence of dynamic hyperinflation, abnormal gas exchange and ventilatory limitation despite cardiac reserve. The CPET clarified the physiological process underpinning the patient's dyspnoea and limiting the patient's activities. This, in turn, helped the clinician tailor the patient's management plan.

Mechanisms of gas transfer impairment utilizing nitric oxide following severe COVID-19 pneumonitis.

Reduced carbon monoxide diffusing capacity (DLCO ) is common after recovery from severe COVID-19 pneumonitis. The extent to which this relates to alveolar membrane dysfunction as opposed to vascular injury is uncertain. Simultaneous measurement of nitric oxide diffusing capacity (DLNO ) and DLCO can partition gas diffusion into its two components: alveolar-capillary membrane conductance (DmCO ) and capillary blood volume (VC ). We sought to evaluate DmCO and VC in the early and later recovery periods after severe COVID-19. Patients attended for post-COVID-19 clinical review and lung function testing including DLNO /DLCO . Repeat testing occurred when indicated and comparisons made using t-tests. Forty-nine (eight female) subjects (mean ± SD age: 58 ± 13, BMI: 34 ± 8) who had severe COVID-19 pneumonitis, WHO severity classification of 6 ± 1, and prolonged (21 ± 22 days) hospital stay, were assessed 2 months (61 ± 35 days) post discharge. DLCO adj (z-score -1.70 ± 1.49, 25/49 < lower limit of normal [LLN]) and total lung capacity (z-score -1.71 ± 1.30) were both reduced. DmCO and VC and were reduced to a similar extent (z-score -1.19 ± 1.05 and -1.41 ± 1.20, p = 0.4). Seventeen (one female) patients returned for repeat testing 4 months (122 ± 61 days) post discharge. In this subgroup with more impaired lung function, DLCO adj improved but remained below LLN (z-score -3.15 ± 0.83 vs. -2.39 ± 0.86, p = 0.01), 5/17 improved to >LNN. DmCO improved (z-score -2.05 ± 0.89 vs. -1.41 ± 0.78, p = 0.01) but VC was unchanged (z-score -2.51 ± 0.55 vs. -2.29 ± 0.59, p = 0.16). Alveolar membrane conductance is abnormal in the earlier recovery phase following severe COVID-19 but significantly improves. In contrast, reduced VC persists. These data raise the possibility that persisting effects of acute vascular injury may contribute to gas diffusion impairment long after severe COVID-19 pneumonitis.

Quality assessment pathway for respiratory oscillometry.

A flow-chart-driven procedure is presented to facilitate respiratory oscillometry operator competency and measurement quality. A novel feature is a quality grading system, in line with other standards of lung function. https://bit.ly/3G4r0X1.

Oscillometry and Asthma Control in Patients With and Without Fixed Airflow Obstruction.

BACKGROUND: Asthma is defined by the presence of reversible airflow limitation, yet persistently abnormal spirometry may develop despite appropriate asthma treatment. Fixed airflow obstruction (FAO) describes abnormal postbronchodilator spirometry that is associated with greater symptom burden and disease severity. Respiratory oscillometry measures the mechanics of the entire airway tree, including peripheral airway changes that have been shown to influence asthma symptoms. OBJECTIVE: To evaluate the relationship between abnormal oscillometry following bronchodilator and symptom control in adults with asthma. METHODS: A prospective cohort of patients with asthma attending an airways clinic completed oscillometry (resistance and reactance), spirometry, and the Asthma Control Test. Postbronchodilator lung function below the lower limit of normal was considered abnormal. Spirometric FAO was defined as FEV1/forced vital capacity below the lower limit of normal. Spearman's rank coefficient and multiple linear regression were performed to assess associations of lung function parameters with Asthma Control Test. The discriminative ability of abnormal lung function to identify poor asthma control was determined using Cohen's kappa. RESULTS: Ninety patients with asthma were included; 48% had spirometric FAO. Only reactance parameters, not spirometry, significantly related to (rs ≥ 0.315; P < .05) and identified asthma control (r2 = 0.236; P < .001). Lung function was more strongly associated with asthma control in patients with FAO compared with those without. Abnormal oscillometry identified an additional 24% of patients with poor asthma control as compared with spirometric FAO. CONCLUSIONS: Reactance related to asthma control, independently of spirometric FAO. Abnormal postbronchodilator reactance identified more patients with poor asthma control compared with spirometry. These findings confirm that oscillometry is a relevant lung function test in the clinical assessment of asthma.

Longitudinal monitoring of asthma in the clinic using respiratory oscillometry.

BACKGROUND AND OBJECTIVE: Asthma guidelines emphasize the importance of assessing lung function and symptoms. The forced oscillation technique (FOT) and its longitudinal relationship with spirometry and symptoms are unresolved. We examined concordance between longitudinal spirometry, FOT and symptom control, and determined FOT limits of agreement in stable asthma. METHODS: Over a 3-year period, adults with asthma attending a tertiary clinic completed the asthma control test (ACT), fraction of exhaled nitric oxide (FeNO), FOT and spirometry. Analysis included between-visit concordance for significant change using Cohen's kappa (κ) and stable asthma FOT limits of agreement. RESULTS: Data (n = 186) from 855 visits (mean ± SD 4.6 ± 3.0 visits), 114 ± 95 days apart, were analysed. Between-visit concordance was moderate between reactance at 5 Hz (X5) and forced expiratory volume in 1 s (FEV1 ) (κ = 0.34, p = 0.001), and weak between ACT and FEV1 (κ = 0.18, p = 0.001). Change in FeNO did not correlate with lung function or ACT (κ < 0.05, p > 0.1). Stable asthma between visits (n = 75; 132 visits) had reduced lung function variability, but comparable concordance to the entire cohort. Limits of agreement for FEV1 (0.42 L), resistance at 5 Hz (2.06 cm H2 O s L-1 ) and X5 (2.75 cm H2 O s L-1 ) in stable asthma were at least twofold greater than published values in health. CONCLUSION: In adults with asthma, there is moderate concordance between longitudinal change in FOT and spirometry. Both tests relate poorly to changes in asthma control, highlighting the need for multi-modal assessment in asthma rather than symptoms alone. The derivation of longitudinal FOT limits of agreement will assist in its clinical interpretation.

Acute cardiopulmonary responses during expert trumpet performance.

Lung function and vascular effects of expert trumpet performance has not been elucidated. Airway mechanics, gas exchange and cardiovascular function were investigated in expert trumpeters during a challenging performance. Respiratory impedance was measured in expert trumpeters and violinist controls prior to and following performance. Electrocardiography, pulse oximetry, transcutaneous CO2 and pulse transit time were monitored continuously. Performance did not alter lung function or gas exchange, except for a reduction in transcutaneous CO2 in 14 expert trumpeters compared to 4 expert violinists. Heart rate variability and pulse transit time were significantly altered in the trumpeters only, associated with the performance ventilatory requirements with a weight to low frequency band reflecting elevated baroreflex feedback. Trumpet performance at an expert level does not have an acute effect on airway mechanics and gas exchange was maintained. Repetitive increased intrathoracic pressure during performance resulted in marked heart rate and vagal tone variability. This study reveals the high demands placed on autonomic modulation of the cardiac response to expert trumpet performance.

Effects of adopting the Global Lung Function Initiative 2017 reference equations on the interpretation of carbon monoxide transfer factor.

The recently published Global Lung Function Initiative (GLI) carbon monoxide transfer factor (T LCO) reference equations provide an opportunity to adopt a current, all-age, widely applicable reference set. The aim of this study was to document the effect of changing to GLI from commonly utilised reference equations on the interpretation of T LCO results.33 863 T LCO results (48% female, 88% Caucasian, n=930 aged <18 years) from clinical pulmonary function laboratories within three Australian teaching hospitals were analysed. The lower limit of normal (LLN) and proportion of patients with a T LCO below this value were calculated using GLI and other commonly used reference equations.The average T LCO LLN for GLI was similar or lower than the other equations, with the largest difference seen for Crapo equations (median: -1.25, IQR: -1.64, -0.86 mmol·min-1·kPa-1). These differences resulted in altered rates of reduced T LCO for GLI particularly for adults (+1.9% versus Miller to -27.6% versus Crapo), more so than for children (-0.8% versus Kim to -14.2% versus Cotes). For adults, the highest raw agreement for GLI was with Miller equations (94.7%), while for children it was with Kim equations (98.1%). Results were reclassified from abnormal to normal more frequently for younger adults, and for adult females, particularly when moving from Roca to GLI equations (30% of females versus 16% of males).The adoption of GLI T LCO reference equations in adults will result in altered interpretation depending on the equations previously used and to a greater extent in adult females. The effect on interpretation in children is less significant.

Bronchodilator Response Assessed by the Forced Oscillation Technique Identifies Poor Asthma Control With Greater Sensitivity Than Spirometry.

BACKGROUND: Persistent bronchodilator response (BDR) following diagnosis of asthma is an underrecognized treatable trait, associated with worse lung function and asthma control. The forced oscillation technique (FOT) measures respiratory system impedance, and BDR cutoffs have been proposed for healthy adults; however, the relevance in asthma is unknown. We compared BDR cutoffs, using FOT and spirometry, in asthma and the relationship with asthma control. METHODS: Data from patients with asthma who withheld bronchodilator medication for at least 8 h before a tertiary airway clinic visit were reviewed. All subjects performed FOT and spirometry before and after salbutamol administration, and completed the Asthma Control Test. FOT parameters examined included respiratory system resistance (R5) and reactance (X5) at 5 Hz, and area under the reactance curve (AX). BDR was defined by standard recommendations for spirometry and based on the 95th percentile of BDR in healthy adults for FOT. RESULTS: Fifty-two subjects (18 men; mean age, 53 ± 18 years) were included. BDR was identified more frequently by FOT than spirometry (54% vs 27% of subjects). BDR assessed by X5 and AX, but not R5, was associated with spirometric BDR (χ2, P < .01) and correlated with asthma control (X5: rs = -0.36, P < .01; AX: rs = 0.34, P = .01). BDR measured by reactance parameters identified more subjects with poor asthma control than did spirometry (AX, 69% vs spirometry, 41%). CONCLUSIONS: BDR assessed by FOT can identify poor asthma control. Reactance parameters were more sensitive in identifying poor asthma control than spirometry, supporting the use of FOT to complement spirometry in the clinical management of asthma.

Exercise-Induced Bronchoconstriction Identified Using the Forced Oscillation Technique.

Objective: Lung mechanics using the forced oscillation technique (FOT) is suggested to be equivalent and more sensitive in determining exercise-induced bronchoconstriction (EIB) than spirometry. Dynamic alterations in minute ventilation (VE) may affect this measurement. We investigated changes in FOT parameters post exercise challenge (EC) in people with asthma as compared to spirometry. The rate of recovery and any effect of raised VE following exercise on FOT parameters were also assessed. Method: Airway resistance (R5) and reactance (X5) at 5 Hz and VE were measured prior to forced expiratory volume in 1 s (FEV1) before and up to 20 min after a standard EC in people with asthma and healthy controls. Airway hyperresponsiveness to the hyperosmolar mannitol test was measured in the asthmatic subjects within 1 week of the EC. Baseline and sequential measures were assessed using repeated measures ANOVA and Pearson's correlation. Group demographics and recovery data were compared using an unpaired t test. Results: Subjects with current asthma (n = 19, mean ± SD age 28 ± 6 years) and controls (n = 10, 31 ± 5 years) were studied. Baseline FEV1, R5, X5, and VE were similar between groups (p > 0.09). Airway hyperresponsiveness was present in 12/19 asthmatic subjects. The EC max % change of R5 and X5 correlated with FEV1 (r > 0.90) and were only different to controls in those with asthma that responded by FEV1 criteria (p < 0.01). EC recovery of R5 was similar to FEV1; however, X5 was greater (p = 0.03). Elevated VE post EC did not affect the % change in FOT parameters across all subjects (p > 0.3). R5 and X5 were highly sensitive in determining a positive EC response (80-86%), but X5 was more specific (93 vs. 80%). Conclusion: FOT parameters tracked with forced maneuvers and were not influenced by increased ventilation following an exercise challenge designed to elicit EIB. FOT identified EIB similarly to spirometry in patients with asthma.

Mepolizumab improves small airway function in severe eosinophilic asthma.

BACKGROUND AND OBJECTIVE: Treatment with mepolizumab in severe eosinophilic asthma (SEA) significantly reduces exacerbations with modest improvements in symptom control and spirometry. The time course of any changes in small airway function is unknown. OBJECTIVE: To describe changes in ventilation inhomogeneity, a marker of small airway function, after commencing mepolizumab. METHODS: Prospective cohort of 20 adults (12 male) with SEA commencing monthly mepolizumab. Measurements at baseline, Week 4 and Week 26 included the Asthma Control Questionnaire (ACQ-5), spirometry, fraction of exhaled nitric oxide (FeNO) and multiple breath nitrogen washout to measure global (Lung Clearance Index, [LCI]) and regional ventilation inhomogeneity in acinar (Sacin) and conducting (Scond) airways. Other asthma therapy remained unchanged between baseline and Week 4. Treatment related changes were assessed using RM-ANOVA and paired t-tests. Relationships between changes in lung function and symptoms were assessed by Pearson's correlation. RESULTS: At Week 4, ACQ-5, spirometry, LCI and Sacin improved significantly (p < 0.04) and all were sustained at Week 26. The change in ACQ-5 correlated with the change in Sacin (r = 0.48, p = 0.03) and FRC (r = 0.46, p = 0.04), but not spirometry. CONCLUSION: Improved symptom control improved rapidly after commencing mepolizumab in patients with SEA. The early improvement in small airway function was associated with asthma control and may be a significant contributor to the therapeutic response.

Exercise-induced Bronchoconstriction with Firefighting Contained Breathing Apparatus.

PURPOSE: Protective self-contained breathing apparatus (SCBA) used for firefighting delivers decompressed (cold) dehumidified air that may enhance the severity of exercise-induced bronchoconstriction (EIB) in those susceptible. We investigated the effect of SCBA during exercise on airway caliber in people with asthma and healthy controls. METHODS: Two exercise challenges (EC) designed to elicit EIB were performed on separate days within 1 wk. The initial challenge was breathing room air (ECRA) with workload titrated to elicit >60% estimated maximum voluntary ventilation. The exercise intensity was repeated for the second challenge using SCBA (ECSCBA). Forced expiratory volume in 1 s (FEV1) was measured before and up to 20 min after exercise. Bronchial hyperresponsivenss (BHR) to the hyperosmolar mannitol test was measured in the subjects with asthma. RESULTS: Twenty subjects with current asthma (mean [SD]: age 27 [6] yr) and 10 healthy controls (31 [5] yr, P = 0.1) were studied. The percent fall in FEV1 after ECSCBA was greater in the mannitol-positive asthma subjects (14.4% [15.1%]) compared with mannitol-negative asthmatic subjects (1.6% [1.7%]; P = 0.02) and controls (2.3% [2.3%]; P = 0.04). The FEV1 response was not different between ECRA and ECSCBA (0.49% [5.57%]; P = 0.6). No BHR to mannitol (n = 7) was highly sensitive for identifying a negative response to ECSCBA (negative predictive value 100%). CONCLUSIONS: The SCBA does not increase the propensity or severity for EIB in subjects with BHR. Those subjects with asthma but no BHR to inhaled mannitol did not exhibit EIB. The BHR to a hyperosmolar stimulus maybe considered a useful screening tool for potential recruits with a history of asthma.

Right heart function during simulated altitude in patients with pulmonary arterial hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. METHODS: Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. RESULTS: The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). CONCLUSIONS: Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function.

Measurement duration impacts variability but not impedance measured by the forced oscillation technique in healthy, asthma and COPD subjects.

The forced oscillation technique (FOT) is gaining clinical acceptance, facilitated by more commercial devices and clinical data. However, the effects of variations in testing protocols used in FOT data acquisition are unknown. We describe the effect of duration of data acquisition on FOT results in subjects with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls. FOT data were acquired from 20 healthy, 22 asthmatic and 18 COPD subjects for 60 s in triplicate. The first 16, 30 and 60 s of each measurement were analysed to obtain total, inspiratory and expiratory resistance of respiratory system (Rrs) and respiratory system reactance (Xrs) at 5 and 19 Hz. With increasing duration, there was a decrease in total and expiratory Rrs for healthy controls, total and inspiratory Rrs for asthmatic subjects and magnitude of total and inspiratory Xrs for COPD subjects at 5 Hz. These decreases were small compared to the differences between clinical groups. Measuring for 16, 30 and 60 s provided ≥3 acceptable breaths in at least 90, 95 and 100% of subjects, respectively. The coefficient of variation for total Rrs and Xrs also decreased with duration. Similar results were found for Rrs and Xrs at 19 Hz. FOT results are statistically, but likely minimally, impacted by acquisition duration in healthy, asthmatic or COPD subjects.

The impact of severe lung disease on evidential breath analysis collection.

BACKGROUND: It is a legal requirement to supply a breath analysis sample when requested by Police at roadside checkpoints. The current device requires a 1L sample at 8L·min(-1). Court disputes commonly attribute respiratory disease for failure to produce a sample. OBJECTIVE: To determine whether respiratory disease aetiology and/or severity precludes an adequate breath sample using a modern evidential breath analyser. METHODS: Subjects performed breath analysis following standard Police procedure. Three efforts within 15min were allowed and any reasons for failure recorded. RESULTS: 24 subjects with interstitial lung disease (ILD) and 26 subjects with chronic obstructive pulmonary disease (COPD) were studied and met minimum respiratory function criteria as per device specifications. 18 ILD subjects (75%) and 24 COPD subjects (92%) were able to provide a sample. All subjects with a vital capacity below 1.5L were unable to provide a sample. DISCUSSION: In the balance of probabilities most patients with lung disease are able to supply an evidential breath sample. The exception is a very severe disease, particularly in volume limited patients.

Physiology in medicine: acute altitude exposure in patients with pulmonary and cardiovascular disease.

Travel is more affordable and improved high-altitude airports, railways, and roads allow rapid access to altitude destinations without acclimatization. The physiology of exposure to altitude has been extensively described in healthy individuals; however, there is a paucity of data pertaining to those who have reduced reserve. This Physiology in Medicine article discusses the physiological considerations relevant to the safe travel to altitude and by commercial aircraft in patients with pulmonary and/or cardiac disease.