Beno W. Oppenheimer

Distal Airway Function Assessed by Oscillometry at Varying Respiratory Rate: Comparison with Dynamic Compliance

Distal airways disease causes significant morbidity yet remains insufficiently identified. We hypothesize that: (1) when spirometry is normal impulse oscillometry may provide information about mechanical properties of the distal airways in a manner comparable to dynamic compliance and (2) variation of breathing frequency will influence oscillometric measurements similar to effects of breathing frequency on dynamic compliance. Fifty-three symptomatic subjects with normal large airway function (spirometry) were studied; distal airway dysfunction was identified by presence of frequency dependence of compliance (FDC). Oscillometric parameters evaluated were resistance at 20 Hz (R20) and 5–20 Hz (R5 − 20), reactance at 5Hz (X5), and reactance area (AX). R20 correlated with airway resistance by esophageal manometry (r = 0.74, p< 0.001); X5 correlated with dynamic compliance at a respiratory rate of 60bpm (r = 0.61, p< 0.001); R5-20 and AX correlated with FDC (r = 0.48, p< 0.001; r = 0.53, p< 0.01). IOS indices were further evaluated at increased respiratory rate (RR40). Oscillometric parameters changed minimally at RR40 in normal subjects ΔR20 = 0.20 = 0.08 cmH2O/L/s, ΔR5-20 = 0.10 ± 0.03 cmH2O/L/s, Δ AX = 0.33 ± 0.19 cmH2O/L). However, in symptomatic subjects, while R20 increased minimallyat RR40 (Δ R20 = 0.37 ± 0.10 cmH2O/L/s), R5 − 20 and AX increased markedly (Δ R5 − 20 = 0.54 ± 0.06 cmH2O/L/s, Δ AX = 4.28 ± 0.67 cmH2O/L) and reversed post bronchodilator. IOS evaluates physiology of the distal airways in a manner comparable to dynamic compliance. Elevated respiratory rate influences oscillometric parameters and must be considered when interpreting oscillometric data. IOS provides a non-invasive tool for assessment of distal airway function when spirometry is normal, which can be applied to various clinical settings including early diagnosis of COPD (GOLD stage 0), asthma in clinical remission and occupational/ environmental irritant exposure.

Lessons From the World Trade Center Disaster: Airway Disease Presenting as Restrictive Dysfunction

BACKGROUND The present study (1) characterizes a physiologic phenotype of restrictive dysfunction due to airway injury and (2) compares this phenotype to the phenotype of interstitial lung disease (ILD). METHODS This is a retrospective study of 54 persistently symptomatic subjects following World Trade Center (WTC) dust exposure. Inclusion criteria were reduced vital capacity (VC), FEV1/VC>77%, and normal chest roentgenogram. Measurements included spirometry, plethysmography, diffusing capacity of lung for carbon monoxide (Dlco), impulse oscillometry (IOS), inspiratory/expiratory CT scan, and lung compliance (n=16). RESULTS VC was reduced (46% to 83% predicted) because of the reduction of expiratory reserve volume (43%±26% predicted) with preservation of inspiratory capacity (IC) (85%±16% predicted). Total lung capacity (TLC) was reduced, confirming restriction (73%±8% predicted); however, elevated residual volume to TLC ratio (0.35±0.08) suggested air trapping (AT). Dlco was reduced (78%±15% predicted) with elevated Dlco/alveolar volume (5.3±0.8 [mL/mm Hg/min]/L). IOS demonstrated abnormalities in resistance and/or reactance in 50 of 54 subjects. CT scan demonstrated bronchial wall thickening and/or AT in 40 of 54 subjects; parenchymal disease was not evident in any subject. Specific compliance at functional residual capacity (FRC) (0.07±0.02 [L/cm H2O]/L) and recoil pressure (Pel) at TLC (27±7 cm H2O) were normal. In contrast to patients with ILD, lung expansion was not limited, since IC, Pel, and inspiratory muscle pressure were normal. Reduced TLC was attributable to reduced FRC, compatible with airway closure in the tidal range. CONCLUSIONS This study describes a distinct physiologic phenotype of restriction due to airway dysfunction. This pattern was observed following WTC dust exposure, has been reported in other clinical settings (eg, asthma), and should be incorporated into the definition of restrictive dysfunction.

Effect of Circulatory Congestion on the Components of Pulmonary Diffusing Capacity in Morbid Obesity

Objective: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (DLCO) and capillary blood volume (Vc) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (Dm) is uncertain. We examined DLCO and its partition into Vc and Dm in 13 severely obese subjects (BMI = 51 ± 14 kg/m2) without manifest cardiopulmonary disease before and after surgically induced weight loss.

Airway Dysfunction in Obesity: Response to Voluntary Restoration of End Expiratory Lung Volume

Introduction Abnormality in distal lung function may occur in obesity due to reduction in resting lung volume; however, airway inflammation, vascular congestion and/or concomitant intrinsic airway disease may also be present. The goal of this study is to 1) describe the phenotype of lung function in obese subjects utilizing spirometry, plethysmography and oscillometry; and 2) evaluate residual abnormality when the effect of mass loading is removed by voluntary elevation of end expiratory lung volume (EELV) to predicted FRC. Methods 100 non-smoking obese subjects without cardio-pulmonary disease and with normal airflow on spirometry underwent impulse oscillometry (IOS) at baseline and at the elevated EELV. Results FRC and ERV were reduced (44±22, 62±14% predicted) with normal RV/TLC (29±9%). IOS demonstrated elevated resistance at 20 Hz (R20, 4.65±1.07 cmH2O/L/s); however, specific conductance was normal (0.14±0.04). Resistance at 5–20 Hz (R5−20, 1.86±1.11 cmH2O/L/s) and reactance at 5 Hz (X5, −2.70±1.44 cmH2O/L/s) were abnormal. During elevation of EELV, IOS abnormalities reversed to or towards normal. Residual abnormality in R5−20 was observed in some subjects despite elevation of EELV (1.16±0.8 cmH2O/L/s). R5−20 responded to bronchodilator at baseline but not during elevation of EELV. Conclusions This study describes the phenotype of lung dysfunction in obesity as reduction in FRC with airway narrowing, distal respiratory dysfunction and bronchodilator responsiveness. When R5−20 normalized during voluntary inflation, mass loading was considered the predominant mechanism. In contrast, when residual abnormality in R5−20 was demonstrable despite return of EELV to predicted FRC, mechanisms for airway dysfunction in addition to mass loading could be invoked.

Disparity Between Proximal and Distal Airway Reactivity During Methacholine Challenge

There is an increasing awareness of the role of distal airways in the pathophysiology of obstructive lung diseases including asthma and chronic obstructive pulmonary disease. We hypothesize that during induced bronchoconstriction: 1) disparity between distal and proximal airway reactivity may occur; and 2) changes in distal airway function may explain symptom onset in subjects with minimal FEV1 change. 185 subjects underwent methacholine challenge testing (MCT). In addition to spirometry, oscillometry was performed at baseline and after maximum dose of methacholine; 33/185 also underwent oscillometry after each dose. Oscillometric parameters included resistance at 5 and 20 Hz (R5, R20) and heterogeneity of distal airway mechanics assessed by frequency dependence of resistance 5–20 Hz (R5–20) and reactance area (AX). R5 varied widely during MCT (range -0.8 – 11.3 cmH2O/L/s) and correlated poorly with change in FEV1 (r = 0.17). Changes in R5 reflected changes in both R20 and R5–20 (r = 0.59, p<0.05; r = 0.87, p<0.0001). However, R20 increased only 0.3 cmH2O/L/s, while R5–20 increased 0.7 cmH2O/L/s for every 1cmH2O/L/s change in R5, indicating predominant effect of distal airway mechanics. 9/33 subjects developed symptoms despite minimal FEV1 change (<5%), while R5 increased 42% due to increased distal airway heterogeneity. These data indicate disparate behavior of proximal airway resistance (FEV1 and R20) and distal airway heterogeneity (R5–20 and AX). Distal airway reactivity may be associated with methacholine-induced symptoms despite absence of change in FEV1. This study highlights the importance of disparity between proximal and distal airway behavior, which has implications in understanding pathophysiology of obstructive pulmonary diseases and their response to treatment.

Potential Mechanism for Transition Between Acute Hypercapnia During Sleep to Chronic Hypercapnia During Wakefulness in Obstructive Sleep Apnea

This paper presents a series of experiments, both in patients and computer models, investigating the transition from acute to chronic hypercapnia in OSA. The data demonstrate that acute hypercapnia during periodic breathing occurs due to either reduction in magnitude of inter-event ventilation and/or reduction in inter-event ventilatory duration relative to duration of the preceding event. The transition between acute hypercapnia during sleep and chronic sustained hypercapnia during wakefulness may be determined by an interaction between respiratory control and renal handling of HCO3-.

Distal airway dysfunction identifies pulmonary inflammation in asymptomatic smokers

Smoking induced inflammation leads to distal airway destruction. However, the relationship between distal airway dysfunction and inflammation remains unclear, particularly in smokers prior to the development of airway obstruction. Seven normal controls and 16 smokers without chronic obstructive pulmonary disease (COPD) were studied. Respiratory function was assessed using the forced oscillation technique (FOT). Abnormal FOT was defined as elevated resistance at 5 Hz (R5). Parameters reflecting distal lung function included frequency dependence of resistance (R5–20) and dynamic elastance (X5). Inflammation was quantified in concentrated bronchoalveolar lavage utilising cell count differential and cytokines expressed as concentration per mL epithelial lining fluid. All control subjects and seven smokers had normal R5. Nine smokers had elevated R5 with abnormal R5–20 and X5, indicating distal lung dysfunction. The presence of abnormal FOT was associated with two-fold higher lymphocyte and neutrophil counts (p<0.025) and with higher interleukin (IL)-8, eotaxin and fractalkine levels (p<0.01). Reactivity of R5–20 and X5 correlated with levels of IL-8, eotaxin, fractalkine, IL-12p70 and transforming growth factor-α (r>0.47, p<0.01). Distal airway dysfunction in smokers without COPD identifies the presence of distal lung inflammation that parallel reported observations in established COPD. These findings were not evident on routine pulmonary function testing and may allow the identification of smokers at risk of progression to COPD. Isolated dysfunction in distal airways identifies pulmonary inflammation in asymptomatic smokers with normal airflow http://ow.ly/8bVk305aVkj

Distal airway dysfunction in obese subjects corrects after bariatric surgery

BACKGROUND Obesity is frequently associated with respiratory symptoms despite normal large airway function as assessed by spirometry. However, reduced functional residual capacity and expiratory reserve volume are common and might reflect distal airway dysfunction. Impulse oscillometry (IOS) might identify distal airway abnormalities not detected using routine spirometry screening. Our objective was to test the hypothesis that excess body weight will result in distal airway dysfunction detected by IOS that reverses after bariatric surgery. The setting was a university hospital. METHODS A total of 342 subjects underwent spirometry, plethysmography, and IOS before bariatric surgery. Of these patients, 75 repeated the testing after the loss of 20% of the total body weight. The data from 47 subjects with normal baseline spirometry and complete pre- and postoperative data were analyzed. RESULTS IOS detected preoperative distal airway dysfunction despite normal spirometry findings by an abnormal airway resistance at an oscillation frequency of 20 Hz (4.75 ± 1.2 cm H2O/L/s), frequency dependence of resistance from 5 to 20 Hz (2.20 ± 1.6 cm H2O/L/s), and reactance at 5 Hz (-3.47 ± 2.1 cm H2O/L/s). Postoperatively, the subjects demonstrated 57% ± 15% excess weight loss. The body mass index decreased (from 44 ± 6 to 32 ± 5 kg/m2, P < .001). Improvements in functional residual capacity (from 59% ± 11% to 75% ± 20% predicted, P < .001) and expiratory reserve volume (from 41% ± 20% to 75% ± 20% predicted, P < .001) were demonstrated. Distal airway function also improved: airway resistance at an oscillation frequency of 20 Hz (3.91 ± .9, P < .001), frequency dependence of resistance from 5 to 20 Hz (1.17 ± .9, P < .001), and reactance at 5 Hz (-1.85 ± .9, P < .001). CONCLUSION The present study detected significant distal airway dysfunction despite normal preoperative spirometry findings. The effect of increased body weight was likely the main mechanism for these abnormalities. However, the inflammatory state of obesity or associated respiratory disease could also be invoked. These abnormalities improved significantly toward normal after weight loss. The results of the present study highlight the importance of bariatric surgery as an effective intervention in reversing these respiratory abnormalities.

POINT: Should Oscillometry Be Used to Screen for Airway Disease? Yes

Detection of airway disease by physiologic testing was initially described using spirometry to determine vital capacity and expiratory airfl ow under maximal eff ort to distinguish obstructive from restrictive disease processes. 1 Subsequently, Dubois and colleagues 2 demonstrated direct assessment of airway resistance using plethysmography and in a separate publication described the precursor of the forced oscillation technique to measure respiratory system resistance. 3 Th is review addresses the question of whether direct assessment of resistance by forced oscillation provides diagnostic information equivalent or superior to standard assessment of airfl ow rates by spirometry.

Isolated small airway reactivity during bronchoprovocation as a mechanism for respiratory symptoms in WTC dust-exposed community members

INTRODUCTION Small airway dysfunction occurs following WTC dust exposure, but its role in producing symptoms is unclear. METHODS Methacholine challenge (MCT) was used to assess the relationship between onset of respiratory symptoms and small airway abnormalities in 166 symptomatic WTC dust-exposed patients. Forced oscillation testing (FOT) and respiratory symptoms were assessed during MCT. FOT parameters included resistance at 5 and 20 Hz (R5 and R20 ) and the R5 minus R20 (R5-20 ). RESULTS Baseline spirometry was normal in all (mean FEV1 100 + 13% predicted, mean FEV1 /FVC 80 + 4%). MCT revealed bronchial hyperreactivity by spirometry in 67 patients. An additional 24 patients became symptomatic despite minimal FEV1 change (<5%); symptom onset coincided with increased R5 and R5-20 (P > 0.001 vs. baseline). The dose-response of FOT (reactivity) was greater compared with subjects that remained asymptomatic (P < 0.05). CONCLUSIONS FOT during MCT uncovered reactivity in small airways as a mechanism for respiratory symptoms in subjects with inhalational lung injury. Am. J. Ind. Med. 59:767-776, 2016.