What constitutes an obstructive ventilatory impairment in a pediatric population? A study design.

INTRODUCTION: There is no clear consensus as to what constitutes an obstructive ventilatory impairment (OVI) in pediatric populations. AIM: To determine the percentage of children/adolescents having an OVI among those addressed for spirometry after taking into account the definitions advanced by some international scholarly societies [British Columbia (BC), British thoracic-society (BTS), Canadian thoracic society (CTS), European respiratory society and American thoracic society (ERS-ATS), global initiative for asthma (GINA), Irish college of general practitioners (ICGP), national asthma council (NAC), national institute of clinical excellence (NICE), Société de pneumologie de langue française, Société pédiatrique de pneumologie et allergologie (SPLF-SP2A), and South African thoracic society (SATS)]. METHODS: This bi-centric cross-sectional study involves two medical structures in Sousse/Tunisia, and will encompass children/adolescents aged 6-18 years. A medical questionnaire will be administered, clinical and anthropometric data will be collected, and the spirometric data will be measured by two spirometers. The following six definitions of OVI will be applied: i) GINA: Forced expiratory volume in 1 second (FEV1) < 80% and a FEV1/forced vital capacity (FVC) ≤ 0.90; ii) ICGP: FEV1/FVC < 0.70; iii) ERS-ATS or BTS or SATS or SPLF-SP2A or NAC: FEV1/FVC z-score < -1.645; iv) NICE: FEV1/FVC < 0.70 or FEV1/FVC z-score < -1.645; v) CTS: FEV1/FVC < 0.80 or a FEV1/FVC z-score < -1.645; and vi) ERS: "FEV1 z-score or FEV1/FVC z-score" < -1.645 or "FEV1 or FEV1/FVC" < 0.80. EXPECTED RESULTS: The percentage of children/adolescents having an OVI will significantly vary between the six definitions. CONCLUSION: The frequency of OVI in a pediatric population will depend on the definition chosen.

Combined obstructive airflow limitation associated with interstitial lung diseases (O-ILD): the bad phenotype ?

BACKGROUND: Patients suffering from combined obstructive and interstitial lung disease (O-ILD) represent a pathological entity which still has to be well clinically described. The aim of this descriptive and explorative study was to describe the phenotype and functional characteristics of a cohort of patients suffering from functional obstruction in a population of ILD patients in order to raise the need of dedicated prospective observational studies and the evaluation of the impact of anti-fibrotic therapies. METHODS: The current authors conducted a retrospective study including 557 ILD patients, with either obstructive (O-ILD, n = 82) or non-obstructive (non O-ILD, n = 475) pattern. Patients included were mainly males (54%) with a mean age of 62 years. RESULTS: Patients with O-ILD exhibited a characteristic functional profile with reduced percent predicted forced expired volume in 1 s (FEV1) [65% (53-77) vs 83% (71-96), p < 0.00001], small airway involvement assessed by maximum expiratory flow (MEF) 25/75 [29% (20-41) vs 81% (64-108), p < 0.00001], reduced sGaw [60% (42-75) vs 87% (59-119), p < 0.01] and sub-normal functional residual capacity (FRC) [113% (93-134) vs 92% (75-109), p < 0.00001] with no impaired of carbon monoxide diffusing capacity of the lung (DLCO) compared to those without obstruction. Total lung capacity (TLC) was increased in O-ILD patients [93% (82-107) vs 79% (69-91), p < 0.00001]. Of interest, DLCO sharply dropped in O-ILD patients over a 5-year follow-up. We did not identify a significant increase in mortality in patients with O-ILD. Interestingly, the global mortality was increased in the specific sub-group of patients with O-ILD and no progressive fibrosing ILD phenotype and in those with connective tissue disease associated ILD especially in case of rheumatoid arthritis. CONCLUSIONS: The authors individualized a specific functional-based pattern of ILD patients with obstructive lung disease, who are at risk of increased mortality and rapid DLCO decline over time. As classically those patients are excluded from clinical trials, a dedicated prospective study would be of interest in order to define more precisely treatment response of those patients.

Use of flow volume curve to evaluate large airway obstruction.

The flow volume loop (FVL) is a graphic display of airflow against lung volumes at different levels obtained during the maximum inspiratory and expiratory maneuver. It is a simple and reproducible method of lung function assessment. A narrative review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed, EMBASE, Ovid MEDLINE and CINAHL databases were queried and reviewed for studies pertinent to the various FVLs abnormalities and their mechanisms from January 2020 to December 2020. We used the following search terms; flow-volume loop, upper airway obstruction, Obstructive airway disease, and spirometry.  Assessing the shape of the flow-volume loop is particularly helpful in diagnosing and localizing upper airway obstruction. They are also helpful in identifying bronchodilator response to treatment. Characteristic FVLs is also seen in patients with obstructive or restrictive lung disorders. Spirometry should be interpreted using the absolute values for flows and volumes as well as the flow volume and volume time curves.

Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study.

BACKGROUND: Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD. METHODS: WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV1 < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description. RESULTS: N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD. CONCLUSIONS: REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

Lung Function Predicts Outcome in Children With Obstructive Lung Disease After Hematopoietic Stem Cell Transplantation.

Obstructive lung disease (OLD) that develops after hematopoietic stem cell transplantation (HSCT) has a significant impact on morbidity and mortality. We investigated the role of pulmonary function tests (PFTs) in the prediction of prognosis of OLD in children who have undergone HSCT. We retrospectively reviewed 538 patients who underwent allogenic HSCT in the Department of Pediatrics, Seoul St. Mary's Hospital, South Korea, from April 2009 to July 2017. OLD was identified on PFTs or chest computed tomography scans obtained from 3 months after HSCT onwards. OLD developed after HSCT in 46 patients (28 male individuals, median age: 11.2 y). The group that developed OLD with an unfavorable prognosis (n=23) had a lower forced vital capacity (FVC) (% of predicted, 78.53±24.00 vs. 97.71±16.96, P=0.01), forced expiratory volume in 1 second (FEV1) (% of predicted, 52.54±31.77 vs. 84.44±18.59, P=0.00), FEV1/FVC (%, 59.28±18.68 vs. 79.94±9.77, P=0.00), and forced expiratory flow at 25% to 75% of forced vital capacity (FEF25-75) (% of predicted, 30.95±39.92 vs. 57.82±25.71, P=0.00) at diagnosis than the group that developed OLD with a favorable prognosis (n=23). The group that developed OLD with an unfavorable prognosis had significant reductions in FVC, FEV1, FEV1/FVC, and FEF25-75 at 2 years after diagnosis. Children who develop OLD with an unfavorable prognosis after HSCT already have poor lung function at the time of diagnosis. Additional treatment should be considered in patients who develop OLD after HSCT according to their PFTs at diagnosis.

Outcome measures for airway clearance techniques in children with chronic obstructive lung diseases: a systematic review.

BACKGROUND: Airway clearance techniques (ACTs) are an important aspect of the treatment of children with chronic obstructive lung diseases. Unfortunately, a sound evidence base is lacking and airway clearance strategies are largely based on clinical expertise. One of the reasons for the limited evidence is the lack of appropriate outcome measures specifically related to the effectiveness of ACTs. This review discusses all outcome measures applied in previous research in the pediatric population to provide a baseline for future studies. DATA SOURCES: A systematic literature search was performed in PubMed, Web of Science and EMBASE databases. Search terms included chronic obstructive lung diseases and ACTs. STUDY SELECTION: Studies were independently selected by the investigators according to the eligibility criteria. After screening, 49 articles remained for further analysis. RESULTS AND CONCLUSIONS: Data are summarized according to the type of outcome measure. 48 (98%) studies performed pulmonary function tests, 19 (39%) assessed expectorated sputum, 10 (20%) parameters related to disease exacerbation, 8 (16%) oxygenation, 8 (16%) patient-reported outcomes, 5 (10%) exercise capacity and 5 (10%) applied imaging techniques. The synthesis of results showed a high discrepancy between studies due to differences in study design, population and the application of techniques. Since no 'gold standard' method could be identified, a combination of different outcome measures is recommended to gain a better understanding and to identify the potential effects of ACTs. An overview of important considerations has been provided to assist researchers in their choice of outcomes in future studies.

Fabry disease during the COVID-19 pandemic. Why and how treatment should be continued.

Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include acroparesthesia, anhydrosis and angiokeratoma, which may present during childhood followed by cardiac, cerebral and renal complications. Even though pulmonary involvement is not widely appreciated by clinicians, an obstructive lung disease is another recognized component of Fabry disease. Coronavirus Disease-19 (COVID-19), caused by the SARS-CoV-2 virus was labeled as a global pandemic and patients with Fabry disease can be considered at high risk of developing severe complications. The impact of COVID-19 on patients with Fabry disease receiving enzyme replacement therapy is still unknown. Many patients who receive treatment in the hospital experienced infusion disruptions due to fear of infection. Effects of temporary treatment interruption was described in more detail in other lysosomal storage diseases, but the recommencement of therapy does not fully reverse clinical decline due to the temporary discontinuation. When possible, home-therapy seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic. Sentence take-home message: Home-therapy, when possible, seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic in patients with Fabry disease.

The need for physiological phenotyping to develop new drugs for airways disease.

Asthma and COPD make up the majority of obstructive airways diseases (OADs), which affects ∼11 % of the population. The main drugs used to treat OADs have not changed in the past five decades, with advancements mainly comprising variations on existing treatments. The recent biologics are beneficial to only specific subsets of patients. Part of this may lie in our inability to adequately characterise the tremendous heterogeneity in every aspect of OAD. The field is currently moving towards the concept of personalised medicine, based on a focus on treatable traits that are objective, measurable and modifiable. We propose extending this concept via the use of emerging clinical tools for comprehensive physiological phenotyping. We describe, based on published data, the evidence for the use of functional imaging, gas washout techniques and oscillometry, as well as potential future applications, to more comprehensively assess and predict treatment response in OADs. In this way, we hope to demonstrate how physiological phenotyping tools will improve the way in which drugs are prescribed, but most importantly, will facilitate development of new drugs for OADs.

[A case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) syndrome]. / Un cas clinique de syndrome d'hyperplasie neuroendocrine pulmonaire diffuse idiopathique (DIPNECH).

INTRODUCTION: DIPNECH is a strictly histological entity according to the WHO 2015 classification and is considered to be at pre-neoplastic risk. It has been proposed that DIPNECH syndrome should be used to describe patients have clinical symptoms, an obstructive ventilatory disorder and compatible radiological abnormalities. The diagnosis is histological and usually based on a surgical lung biopsy. CASE REPORT: We report the case of a 58-year-old woman with a chronic cough for over 20years who had an obstructive airway pattern on spirometry. Diagnoses of asthma and COPD had been discussed. After 7years of follow-up, the DIPNECH hypothesis was evoked on the scanning aspect of mosaic attenuation, expiratory trapping and micronodules, which was subsequently confirmed by surgical pulmonary biopsy. CONCLUSION: It is necessary to consider the possibility of this rare disease in order to avoid inappropriate treatments and in the hope that future therapeutic advances (somatostatin analogs, mTOR inhibitors) improve patients' experience and the progression of respiratory function.

LUNG REGENERATION IN ABSTAINING SMOKERS.

Smoking modifies morphological and physiological parameters of the lungs. Due to the irritation of airways, the natural self-cleaning ability of the lungs is impaired. The mucus accumulates in the airways and various infections develop, leading to chronic bronchitis. After the cessation of smoking, the lungs of the smoker start to heal and regenerate. Cilia in the lungs start to grow again and cleanse the lungs, thus reducing the risk of infection. The regeneration of the lungs takes a long time and depends on the degree of lung damage due to smoking. The aim of this study was to reconstruct the evolution of this regeneration process in chronic smokers by using the biological effects of radon and its decay products. Thus, radon in this study served as a tracer of changes induced by smoking.

Comparison of impedance measured by the forced oscillation technique and pulmonary functions, including static lung compliance, in obstructive and interstitial lung disease.

Objective: To examine whether the parameters of impedance measured by the broadband frequency forced oscillation technique (FOT) were reflected by changes in lung compliance induced by emphysema and fibrosis, we retrospectively compared the parameters of FOT and pulmonary functions, including static lung compliance (Cst), in obstructive lung disease (OLD) and interstitial lung disease (ILD). Patients and methods: The data of 18 patients with OLD (16 with COPD, two with asthma COPD overlap), 11 with ILD, and 24 healthy volunteers, whose respiratory impedance was measured using a MostGraph-01 and other pulmonary functions including Cst and lung resistance (RL) were measured on the same day and were retrospectively collected and compared. Results: The parameters of resistance, reactance, and resonant frequency showed good correlations with ventilation unevenness (r=0.63, -0.89, 0.77, respectively) and lung elastic resistance (r=0.59, -0.80, 0.73, respectively) in all groups (N=53). These indices were significant determinants of increased respiratory resistance and more negative shift of respiratory reactance (Xrs) at lower frequency (P<0.001). Decreased functional residual capacity was also a determinant of Xrs at 5 Hz (X5) (P<0.05). The differences in mean X5 in the expiratory phase relative to those in the inspiratory phase (within-breath changes in X5) were associated with airflow obstruction (P<0.002) and lung elastic resistance (P<0.001). However, no significant correlations between Cst and any parameters of respiratory impedance were observed. Conclusions: These findings suggest that the impedance parameters measured by FOT are reflected by airway obstruction, ventilation unevenness, and lung resistance, but hardly reflected by changes in lung compliance due to emphysema or fibrosis in both CLD and ILD.

Single-breath washout and association with structural lung disease in children with cystic fibrosis.

BACKGROUND: In children with cystic fibrosis (CF) lung clearance index (LCI) from multiple-breath washout (MBW) correlates with structural lung disease. As a shorter test, single-breath washout (SBW) represents an attractive alternative to assess the ventilation distribution, however, data for the correlation with lung imaging are lacking. METHODS: We assessed correlations between phase III slope (SIII) of double-tracer gas SBW, nitrogen MBW indices (LCI and moment ratios for overall ventilation distribution, Scond, and Sacin for conductive and mainly acinar ventilation, respectively) and structural lung disease assessed by chest computed tomography (CT) in children with CF. RESULTS: In a prospective cross-sectional study data from MBW, SBW, and chest CT were obtained in 32 children with CF with a median (range) age of 8.2 (5.2-16.3) years. Bronchiectasis was present in 24 (75%) children and air trapping was present in 29 (91%). Median (IQR) SIII of SBW was -138.4 (150.6) mg/mol. We found no association between SIII with either the MBW outcomes or CT scores (n = 23, association with bronchiectasis extent r = 0.10, P = 0.64). LCI and Scond were associated with bronchiectasis extent (n = 23, r = 0.57, P = 0.004; r = 0.60, P = 0.003, respectively). CONCLUSIONS: Acinar ventilation inhomogeneity measured by SBW was not associated with structural lung disease on CT. Double-tracer SBW added no benefit to indices measured by MBW.

Correlating exhaled aerosol images to small airway obstructive diseases: A study with dynamic mode decomposition and machine learning.

BACKGROUND: Exhaled aerosols from lungs have unique patterns, and their variation can be correlated to the underlying lung structure and associated abnormities. However, it is challenging to characterize such aerosol patterns and differentiate their difference because of their complexity. This challenge is even greater for small airway diseases, where the disturbance signals are weak. OBJECTIVES AND METHODS: The objective of this study is exploiting different feature extraction algorithms to develop a practical classifier to diagnose obstructive lung diseases using exhaled aerosol images. These include proper orthogonal decomposition (POD), principal component analysis (PCA), dynamic mode decomposition (DMD), and DMD with control (DMDC). Aerosol images were generated via physiology-based simulations in one normal and four diseased airway models in G7-9 bronchioles. The image data were classified using both the support vector machine (SVM) and random forest (RF) algorithms. The effectiveness of different features was evaluated by classification accuracy and misclassification rate. FINDINGS: Results show a significantly higher performance using dynamic feature extractions (DMD and DMDC) than static algorithms (POD and PCA). Adding the control variables to DMD further improved classification accuracy. Comparing the classification methods, RF persistently outperformed SVM for all types of features considered. While the performance of RF constantly increased with the number of features retained, the performance of SVM peaked at 50 and decreased thereafter. The 5-class classification accuracy was 94.8% using the DMDC-RF model and 93.0% using the DMD-RF model, both of which were higher than 87.0% in the previous study that used fractal dimension features. CONCLUSION: Considering that disease progression is inherently a dynamic process, DMD(C)-based feature extraction preserves temporal information and is preferred over POD and PCA. Compared with hand-crafted features like fractals, feature extraction by DMD and DMDC is automatic and more accurate.

The prognostic impact of obstructive lung disease on survival of never smokers with resected non-small-cell lung cancer: a comparison with smokers.

OBJECTIVES: The proportion of never smokers among non-small-cell lung cancer (NSCLC) patients has steadily increased in recent decades, suggesting an urgent need to identify the major underlying causes of disease in this cohort. Chronic obstructive pulmonary disease is a risk factor for lung cancer in both smokers and never smokers. The aim of this study was to investigate the association between obstructive lung disease and survival in never smokers and smokers with NSCLC after complete resection. METHODS: We retrospectively reviewed data from 548 NSCLC patients treated at our institution. The effects of obstructive lung disease on recurrence-free survival and cancer-specific survival following the resection of NSCLC were determined by univariable and multivariable Cox regression analyses. RESULTS: Among the 548 patients analysed, 244 patients (44.5%) were never smokers and 304 patients (55.4%) were current or former smokers. In the never-smoker group, 48 patients (19.7%) had obstructive lung disease, 185 patients (75.8%) were women and 226 patients (92.6%) had adenocarcinoma. Obstructive lung disease was significantly associated with shorter recurrence-free survival (P = 0.006) and cancer-specific survival (P = 0.022) in the never smokers, but not the smokers, on both univariable and multivariable analyses. The associations between obstructive lung disease and prognosis in never smokers remained significant after propensity score matching. CONCLUSIONS: Obstructive lung disease is an independent prognostic factor for recurrence-free survival and cancer-specific survival in never smokers, but not in smokers, with NSCLC. Based on this finding, further examination is warranted to advance our understanding of the mechanisms associated with NSCLC in never smokers.

Prevalence and nature of lung function abnormalities among Indigenous Australians referred to specialist respiratory outreach clinics in the Northern Territory.

BACKGROUND: Poor lung function is a predictor of future all-cause mortality. In Australia, respiratory diseases are particularly prevalent among the indigenous population, especially in remote communities. However, there are little published pulmonary function tests' (PFT) data of remote-based adult indigenous patients. AIM: To evaluate the severity of airflow obstruction and other PFT abnormalities of adults referred to specialist respiratory clinics in remote indigenous communities. METHODS: Retrospective analysis of PFT (pre- and post-bronchodilator spirometry, total lung capacity (TLC) and diffusing capacity to carbon monoxide (DLCO)) of indigenous patients collected during specialist respiratory clinics in remote Northern Territory (NT) indigenous communities (Australia) between 2013 and 2015. The National Health and Nutrition Examination Survey (NHANES) III without ethnic correction was used as the reference. RESULTS: Of the 357 patients, 150 had acceptable spirometry, and 71 had acceptable DLCO and TLC studies. Despite the relatively young age (mean = 49 years, SD = 12.9), their lung function was generally low; mean % predicted values were FEV1 = 55% (SD = 20.5%), FVC = 61% (SD = 15.6%), DLCO = 64.0% (SD = 19.7%) and TLC = 70.1% (SD = 18.2%). Mean FEV1 /FVC ratio was preserved (0.71, SD = 0.16). Post-bronchodilator airflow obstruction (FEV1 /FVC < 0.7) was observed in 37% of patients, where a large proportion (67%) demonstrated at least a severe airflow obstruction, with a mean FEV1 of 41% predicted. CONCLUSION: In this first study of PFT findings of indigenous adults from a remote-based clinical service, we found a high rate of at least moderate airflow limitation and low FVC along with preserved FEV1/FVC ratio. Increased awareness and screening for reduced lung function needs to be considered in this population.

A Comparison of Global Lung Initiative 2012 with Third National Health and Nutrition Examination Survey Spirometry Reference Values. Implications in Defining Obstruction.

RATIONALE: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal for the FEV1/FVC ratio. Current established reference values use the Third National Health and Nutrition Examination Survey (NHANES III) database. In 2012, the Global Lung Initiative (GLI) introduced GLI12, which is a compilation reference set that uses standard deviation values to define normal spirometry. OBJECTIVES: To evaluate the changes in classification of obstructive spirometry with use of GLI12 compared with NHANES III in a heterogeneous, multiracial population. METHODS: We evaluated the spirometry studies conducted in our pulmonary function laboratory between January 2005 and December 2015. NHANES III reference equations were calculated to predict lower limits of normal for FEV1, FVC, and FEV1/FVC. GLI12 values were established using European Respiratory Society published computer software. FEV1 severity was graded using 2005 American Thoracic Society guidelines for NHANES III and using z-score-based criteria for GLI12. Asymmetric partition analysis evaluated agreement between the reference sets. RESULTS: A total of 11,888 studies were evaluated. Obstruction was diagnosed in 2,857 studies using NHANES III versus 2,489 studies using GLI12. Agreement regarding the presence or absence of obstruction occurred in 2,483 of studies with obstruction and 9,025 studies without obstruction (agreement, 96.8%; κ = 0.91). Of the studies with obstruction, 1,595 had agreement in severity grading. Overall, agreement regarding obstruction and severity grading occurred in 10,620 studies, representing 89.3% of all studies. A total of 380 studies (3.2%) had discordance regarding the presence or absence of obstruction, 34.0% (844 of the 2,483 obstruction studies) had a one-degree of change in FEV1 disease severity scoring, with 44 cases (1.8%) that had changes of two categories in FEV1 severity scores. No studies had greater than two degrees of change. Asymmetric partition analysis suggested that the highest clinically significant changes were seen in older individuals, particularly African American men older than 65. CONCLUSIONS: Our evaluation suggests that there is moderate overall agreement between NHANES III and GLI12. We found a 3.2% change in classification of obstruction when transitioning from NHANES III to GLI12. When incorporating a z-score-based FEV1 and GLI12 reference set, 10.7% of the spirometry studies had a change in their categorization. The disagreement between the two datasets was most pronounced in elderly subjects. Although we cannot endorse one reference set over the other, we highlight the potential implications of adopting the GLI12 reference sets and suggest caution when interpreting spirometry in the elderly.