The World Trade Center (WTC) destruction released dust and fumes into the environment. Although many community members developed respiratory symptoms, screening spirometry was usually normal. We hypothesised that forced oscillation testing would identify functional abnormalities undetected by spirometry and that symptom severity would relate to magnitude of abnormalities measured by oscillometry. A symptomatic cohort (n=848) from the Bellevue Hospital WTC Environmental Health Center was evaluated and compared to an asymptomatic cohort (n=475) from the New York City Department of Health WTC Health Registry. Spirometry and oscillometry were performed. Oscillometry measurements included resistance (R5) and frequency dependence of resistance (R5-20). Spirometry was normal for the majority of subjects (73.2% symptomatic versus 87.6% asymptomatic, p<0.0001). In subjects with normal spirometry, R5 and R5-20 were higher in symptomatic versus asymptomatic subjects (median (interquartile range) R5 0.436 (0.206) versus 0.314 (0.129) kPa·L-1·s-1, p<0.001; R5-20 0.075 (0.085) versus 0.004 (0.042) kPa·L-1·s-1, p<0.0001). In symptomatic subjects, R5 and R5-20 increased with increasing severity and frequency of wheeze (p<0.05). Measurement of R5-20 correlated with the presence and severity of symptoms even when spirometry was within normal limits. These findings are in accord with small airway abnormalities as a potential explanation of the respiratory symptoms.

Spirometry does not have a short-term effect on multiple-breath washout outcomes, thus allowing greater flexibility for implementation into clinical practice http://ow.ly/2Tg330ngXk4.

Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC).

Diagnosis of asthma in obese individuals frequently relies on clinical history, as airflow by spirometry may remain normal. This study hypothesised that obese subjects with self-reported asthma and normal spirometry will demonstrate distinct clinical characteristics, metabolic comorbidities and enhanced small airway dysfunction as compared with healthy obese subjects. Spirometry, plethysmography and oscillometry data pre/post-bronchodilator were obtained in 357 obese subjects in three groups as follows: no asthma group (n=180), self-reported asthma normal spirometry group (n=126), and asthma obstructed spirometry group (n=51). To assess the effects of obesity related to reduced lung volume, oscillometry measurements were repeated during a voluntary inflation to predicted functional residual capacity (FRC). Dyspnoea was equally prevalent in all groups. In contrast, cough, wheeze and metabolic comorbidities were more frequent in the asthma normal spirometry and asthma obstructed spirometry groups versus the no asthma group (p<0.05). Despite similar body size, oscillometry measurements demonstrated elevated R 5-20 (difference between resistance at 5 and 20 Hz) in the no asthma and asthma normal spirometry groups (0.19±0.12; 0.23±0.13 kPa/(L·s-1), p<0.05) but to a lesser degree than the asthma obstructed spirometry group (0.34±0.20 kPa/(L·s-1), p<0.05). Differences between groups persisted post-bronchodilator (p<0.05). Following voluntary inflation to predicted FRC, R 5-20 in the no asthma and asthma normal spirometry groups fell to similar values, indicating a reversible process (0.11±0.07; 0.12±0.08 kPa/(L·s-1), p=NS). Persistently elevated R 5-20 was seen in the asthma obstructed spirometry group, suggesting chronic inflammation and/or remodelling (0.17±0.11 kPa/(L·s-1), p<0.05). Thus, small airway abnormalities of greater magnitude than observations in healthy obese people may be an early marker of asthma in obese subjects with self-reported disease despite normal airflow. Increased metabolic comorbidities in these subjects may have provided a milieu that impacted airway function.

The diagnosis of COPD requires the demonstration of non-fully reversible airflow limitation by spirometry in the appropriate clinical context. Yet, there are patients with symptoms and relevant exposures suggestive of COPD with either normal spirometry (pre-COPD) or preserved ratio but impaired spirometry (PRISm). Their prevalence, clinical characteristics and associated outcomes in a real-life setting are unclear.

Long-term outcomes after lung transplantation are often limited by the development of obliterative bronchiolitis (OB), which is clinically defined using spirometry as bronchiolitis obliterans syndrome (BOS). Lung clearance index (LCI), derived from multiple breath washout (MBW) testing, is a global measure of ventilation heterogeneity that has previously been shown to be a more sensitive measure of obstructive small airway diseases than spirometry. We aimed to assess the feasibility of LCI in adult lung transplant patients and to compare LCI to BOS grade.

There is a large burden of COPD in the US. The purpose of this study was to investigate the association between diet quality with lung function, spirometric restriction and spirometrically defined COPD in a nationally representative sample of US adults.

Spirometry and testing for bronchodilator response have been recommended to detect asthma, and a bronchodilator response (BDR) of ≥12% and ≥200 mL has been suggested to confirm asthma. However, the clinical value of bronchodilation tests in newly diagnosed steroid-naïve adult patients with asthma remains unknown. We evaluated the sensitivity of BDR in forced expiratory volume in 1 s (FEV1) as a diagnostic test for asthma in a real-life cohort of participants in the Seinäjoki Adult Asthma Study. In the diagnostic phase, 369 spirometry tests with bronchodilation were performed for 219 steroid-naïve patients. The fulfilment of each test threshold was assessed. According to the algorithm of the National Institute for Health and Care Excellence, we divided the patients into obstructive (FEV1/forced vital capacity (FVC) <0.70) and non-obstructive (FEV1/FVC ≥0.70) groups. Of the overall cohort, 35.6% fulfilled ΔFEV1 ≥12% and ≥200 mL for the initial FEV1, 18.3% fulfilled ΔFEV1 ≥15% and ≥400 mL for the initial FEV1, and 36.1% fulfilled ΔFEV1 ≥9% of predicted FEV1 at least once. One-third (31%) of these steroid-naïve patients was obstructive (pre-bronchodilator FEV1/FVC <0.7). Of the obstructive patients, 55.9%, 26.5% and 48.5%, respectively, met the same thresholds. In multivariate logistic regression analysis, different thresholds recognised different kinds of asthma patients. In steroid-naïve adult patients, the current BDR threshold (ΔFEV1 ≥12% and ≥200 mL) has low diagnostic sensitivity (36%) for asthma. In obstructive patients, sensitivity is somewhat higher (56%) but far from optimal. If the first spirometry test with bronchodilation is not diagnostic but asthma is suspected, spirometry should be repeated, and other lung function tests should be used to confirm the diagnosis.

Reversible airway obstruction is common in children with primary ciliary dyskinesia. However, the diagnostic value of adding bronchodilator (BD) response testing to routine spirometry is unclear.

Physiological phenotyping using daily home-based assessments reveals early improvement in load-capacity-drive imbalance following #AECOPD and feasibility of home parasternal electromyography measurement, which tracks symptoms, health status and spirometry https://bit.ly/3o6I0Ty.

Primary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function in PCD patients range from normal to severe impairment. This systematic review and meta-analysis of studies of lung function in PCD patients examines the spirometric indices of PCD patients and differences by age group and sex. We searched PubMed, Embase and Scopus for studies that described lung function in 10 or more patients with PCD. We performed meta-analyses and meta-regression to explain heterogeneity. We included 24 studies, ranging from 13 to 158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 s (FEV1) and forced vital capacity presented as mean and standard deviation of percent predicted values. We found considerable heterogeneity for both parameters (I 2=94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV1 in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.

In smokers with preserved spirometry, D LCO is associated with ventilation inhomogeneity arising from peripheral airways. Measurement of D LCO to screen for early lung function abnormalities in smokers may be suboptimal and could be replaced by MBW. https://bit.ly/3nLmgg1.

Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function.

COPD affects the small airways and is associated with ventilation heterogeneity. There are little data on the multiple-breath washout (MBW) in patients with COPD, particularly the variability over 8 weeks, using a shortened sulfur hexafluoride (SF6) washout. This work evaluated the repeatability of the lung clearance index (LCI)1/40 and LCI1/20 among subjects with COPD and compared to spirometry and clinical markers.

Low body mass index (BMI) and malnutrition in chronic obstructive pulmonary disease (COPD) are associated with a poor prognosis. The prevalence of underweight, as well as overweight, in severity grades of COPD is sparsely investigated in studies of the general population and the associated patterns of risk factors are not well established. The aim of the present study was to determine the association between severity grades of airflow limitation in COPD, and both underweight and obesity when corrected for possible confounding factors. The study is based on pooled data from the OLIN (Obstructive Lung Disease in Northern Sweden) studies. Complete records with lung function, BMI and structured interview data were available from 3942 subjects (50.7% women and 49.3% men). COPD and severity grading were defined using the Global Initiative for Chronic Obstructive Lung Disease criteria. In sensitivity analyses, the lower limit of normal was used. The prevalence of underweight was 7.3% in severe COPD (grades 3 and 4) versus 2.0% in those with normal spirometry. The prevalence of obesity increased from 9.7% in grade 1, to 16.3% in grade 2 and 20.0% in severe COPD, versus 17.7% in those with normal spirometry. In adjusted analysis, of the COPD severity grades, only severe COPD was associated with underweight (OR 3.24, 95% CI 1.0004-10.5), while the COPD severity grades tended to be inversely associated with overweight.

Serial peak expiratory flow (PEF) measurements can identify phenotypes in severe adult asthma, enabling more targeted treatment. The feasibility of this approach in children has not been investigated. Overall, 105 children (67% male, median age 12.4 years) with a range of asthma severities were recruited and followed up over a median of 92 days. PEF was measured twice daily. Fluctuation-based clustering (FBC) was used to identify clusters based on PEF fluctuations. The patients' clinical characteristics were compared between clusters. Three PEF clusters were identified in 44 children with sufficient measurements. Cluster 1 (27% of patients: n=12) had impaired spirometry (mean forced expiratory volume in 1 s (FEV1) 71% predicted), significantly higher exhaled nitric oxide (≥35 ppb) and uncontrolled asthma (asthma control test (ACT) score <20 of 25). Cluster 2 (45%: n=20) had normal spirometry, the highest proportion of difficult asthma and significantly more patients on a high dose of inhaled corticosteroids (≥800 µg budesonide). Cluster 3 (27%: n=12) had mean FEV1 92% predicted, the highest proportion of patients with no bronchodilator reversibility, a low ICS dose (≤400 µg budesonide), and controlled asthma (ACT scores ≥20 of 25). Three clinically relevant paediatric asthma clusters were identified using FBC analysis on PEF measurements, which could improve telemonitoring diagnostics. The method remains robust even when 80% of measurements were removed. Further research will determine clinical applicability.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria for chronic obstructive pulmonary disease (COPD) use a fixed threshold of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (<0.70) in post-bronchodilation spirometry to indicate disease, which has been shown to underestimate and overestimate disease prevalence in younger and older adults, respectively, whilst criteria based on reference values have better accuracy. Differences in reference values have limited their use in international studies. However, the new Global Lung Function Initiative reference values (GLI2012) showed FEV1/FVC to be the least dependent on ethnicity. The aim of this study was to assess the prevalence of airflow limitation with GLI2012 and the degree of underdetection or overestimation related to the use of GOLD in the general population. A Finnish population sample of 1323 subjects (45% male) with post-bronchodilation spirometry was studied. 80 subjects (6.0%) and 55 subjects (4.2%) were identified with airflow limitation with GOLD and GLI2012 criteria, respectively. The proportion of overestimation with GOLD increased with age from 25% of cases in 50-year-olds to 54% in 70-year-olds. Using z-score-based grading resulted in more dispersion in severity grading. In conclusion, the GOLD criteria cause a marked overestimation already from 50-year-olds and should be replaced with the GLI2012 criteria to improve diagnostic accuracy.

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear. We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery. We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery. The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.

Reliable, accurate and noninvasive methods for measuring lung function in infants are desirable. Electromagnetic inductance plethysmography has been used to perform infant spirometry and VoluSense Pediatrics (VSP) (VoluSense, Bergen, Norway) represents an updated version of this technique. We aimed to examine its accuracy compared to a validated system measuring airflow via a facemask using an ultrasonic flowmeter. We tested 30 infants with postmenstrual ages between 36 to 43 weeks and weights from 2.3 to 4.8 kg, applying both methods simultaneously and applying VSP alone. Agreement between the methods was calculated using Bland-Altman analyses and we also estimated the effect of applying the mask. Mean differences for all breathing parameters were within ±5.5% and limits of agreement between the two methods were acceptable, except perhaps for peak tidal expiratory flow (PTEF). Application of the facemask significantly increased tidal volume, minute ventilation, PTEF, the ratio of inspiratory to expiratory time and the ratio of expiratory flow at 50% of expired volume to PTEF. VSP accurately measured tidal breathing parameters and seems well suited for tidal breathing measurements in infants under treatment with equipment that precludes the use of a facemask.

Homozygosity for the SERPINA1 Z allele causes α1-antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on nonrespiratory phenotypes, and on lung function in the general population, remain unclear. We conducted a large, population-based study to determine Z allele effects on >2400 phenotypes in the UK Biobank (N=303 353). Z allele heterozygosity was strongly associated with increased height (β=1.02 cm, p=3.91×10-68), and with other nonrespiratory phenotypes including increased risk of gall bladder disease, reduced risk of heart disease and lower blood pressure, reduced risk of osteoarthritis and reduced bone mineral density, increased risk of headache and enlarged prostate, as well as with blood biomarkers of liver function. Heterozygosity was associated with higher height-adjusted forced expiratory volume in 1 s (FEV1) (β=19.36 mL, p=9.21×10-4) and FEV1/forced vital capacity (β=0.0031, p=1.22×10-5) in nonsmokers, whereas in smokers, this protective effect was abolished. Furthermore, we show for the first time that sex modifies the association of the Z allele on lung function. We conclude that Z allele heterozygosity and homozygosity exhibit opposing effects on lung function in the UK population, and that these associations are modified by smoking and sex. In exploratory analyses, heterozygosity for the Z allele also showed pleiotropic associations with nonrespiratory health-related traits and disease risk.