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Objective: To investigate the correlation between impulse oscillometry system examination indicators and conventional pulmonary ventilation function. Methods: The pulmonary ventilation function data of 10 883 patients from January 1, 2020 to December 31, 2022 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were included. The one-second rate [ratio of forced expiratory volume in the first second (FEV 1 ) to forced vital capacity (FVC)] measured as a percentage of the predicted value was ≥92% for the control group ( n= 3 478) and <92% for the pulmonary obstruction group ( n= 7 405). The obstruction group was subdivided into five groups according to the degree of pulmonary dysfunction: mild group ( n= 3 938),moderate group ( n= 1 142),oderate-severe group ( n= 917),severe group ( n= 737),and extremely severe group ( n= 671). Conventional pulmonary ventilatory function FVC, FEV 1 , one-second rate, and forced expired flow at 50% of FVC (MEF50%), forced expired flow at 75% FVC (MEF25%), maximal mid-expiratory flow (MMEF), peak expiratory flow (PEF), and pulsed oscillation pulmonary function test were detected in both groups of patients. Impedance at 5 Hz (Z5) means total respiratory resistance, resistance at 5 Hz (R5) means total airway resistance, reactance at 5 Hz (X5) indicates the elastic recoil of the peripheral airways, and resistance at 20 Hz (R20) represents resistance of the central airways. R5-R20 reflects resistance in the small airways. Additionally, peripheral resistance (Rp), respiratory resonance frequency (Frex), and area under the reactance curve (Ax) were also measured. Correlation between the indicators of the two groups and the sensitivity and specificity of the impulse oscillometry system parameters for the diagnosis of obstructive pulmonary ventilation dysfunction were analyzed. Results: Pulmonary function force expiratory volume in the first second as a percentage of predicted value (FEV 1 %Pre) [80.10 (54.95,97.10)%],one-second rate [62.43(48.67, 67.02)%],MEF50% [1.33 (0.62,1.97)L/s],MEF25% [0.28 (0.17,0.41)L/s], MMEF [0.85 (0.43,1.29)L/s],and PEF [5.64 (3.73,7.50)]L/s in the obstruction group were significantly lower than those in the control group ( P< 0.05). The differences within the subgroups of the obstruction group were also significant ( P< 0.05). Pulsed oscillation Z5 [0.42 (0.33,0.55)kPa·L -1 ·s -1 ],Rp [0.25 (0.20,0.45)kPa·L -1 ·s -1 ], R5 [0.39 (0.31,0.49)kPa·L -1 ·s -1 ], R20 [0.28 (0.24,0.34)kPa·L -1 ·s -1 ], R5-R20 [0.09 (0.05,0.17)kPa·L -1 ·s -1 ],Frex [16.32 (13.07,20.84)Hz], and Ax [0.67 (0.28,1.64)] indices in the obstruction group were significantly higher than those in the control group. X5 [-0.14 (-0.23, -0.10)kPa·L -1 ·s -1 ] was significantly lower than that in the control group ( P< 0.05). Z5, Rp, X5, R5, R5-R20, Frex, and Ax were statistically significant between different degrees of obstruction in the obstruction group ( P< 0.05). The impulse oscillometry system parameters Z5, Rp, R5, R20, R5-20, Frex, and Ax were negatively correlated with the indices of conventional pulmonary ventilation ( r =-0.21-0.68, P< 0.05), and the parameter X5 was positively correlated with the indices of conventional pulmonary ventilation ( r= 0.41-0.68, P< 0.05). The pulsed oscillation pulmonary function test parameters X5 (58.60%-95.68%) and Ax (57.08%-98.06%) presented the best sensitivity; X5 (86.29%-98.82%), Frex (86.69%-94.71%), and Ax (88.10%-98.53%) displayed the best specificity; and R20 presented the worst sensitivity and specificity. The sensitivity and specificity were slightly better in female patients than in male patients. Conclusion: The technical parameters of the impulse oscillometry system showed significant correlation with relevant indices of conventional pulmonary ventilation function detection. These well reflect the changes of different degrees of pulmonary ventilation function and have greater significance for reference in evaluating the degree of pulmonary function impairment.

Obstructive lung diseases such as bronchial asthma, COPD, and cystic fibrosis are a burden on many patients across the globe. Spirometry is considered the gold standard for diagnosing airflow obstruction, but it can be difficult for pediatric patients to do and requires a lot of effort. As a result, healthcare providers need new, effortless methods to diagnose airway obstructions, particularly in young children and individuals unable to perform the spirometry maneuver. The forced oscillation technique is a modern method requiring only tidal breathing combined with the application of external, source of low-amplitude oscillations to evaluate the respiratory system's response. It might be essential for identifying early respiratory changes caused by smoking, childhood asthma, and may prove more sensitive than spirometry in identifying peripheral airway disturbances or evaluating the long-term success of therapy. This review describes the methodology and the indications for the forced oscillation technique and outlines its relevance in clinical practice., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

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., (© 2022. The Author(s).)

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.

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; FEV 1  < 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.

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.

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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 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., Competing Interests: Declaration of Competing Interest Juan Politei has no conflicts of interest to declare related to this manuscript No funding for this manuscript, (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

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., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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 (R L ) 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., Competing Interests: Prof. Dr. Keisaku Fujimoto reports grants from Koganei Corporation, Murata Manufacturing Co., LTD., Seiko Epson Corporation, Denso Corporation, grants and personal fees from Nippon Boehringer Ingelheim Co., Ltd., personal fees from Astellas Pharma Inc., AstraZeneca K.K., Fukuda Denshi Co., Ltd, Fukuda Lifetec Co., Ltd., Japan Association for the Advancement of Medical Equioment, Japan Respiratory Society, Kyorin Pharmaceutical Co., Ltd, Meiji Seika Pharma Co., Ltd., MSD K.K., Novartis Pharma K.K., Teijin Home Healthcare Limited, and Teijin Pharma Limited, outside the submitted work. The authors report no other conflicts of interest in this work.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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., (© 2019 Wiley Periodicals, Inc.)

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 FEV 1 = 55% (SD = 20.5%), FVC = 61% (SD = 15.6%), DLCO = 64.0% (SD = 19.7%) and TLC = 70.1% (SD = 18.2%). Mean FEV 1 /FVC ratio was preserved (0.71, SD = 0.16). Post-bronchodilator airflow obstruction (FEV 1 /FVC < 0.7) was observed in 37% of patients, where a large proportion (67%) demonstrated at least a severe airflow obstruction, with a mean FEV 1 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., (© 2018 Royal Australasian College of Physicians.)

Rationale: Obstructive lung disease is diagnosed by a decreased ratio of forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity (FVC); however, there is no universally accepted lower limit of normal for the FEV 1 /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 FEV 1 , FVC, and FEV 1 /FVC. GLI12 values were established using European Respiratory Society published computer software. FEV 1 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 FEV 1 disease severity scoring, with 44 cases (1.8%) that had changes of two categories in FEV 1 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 FEV 1 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.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Reduced lung function predicts increased mortality, but its prevalence may vary depending on definition considered, use of bronchodilation and applied reference values. We aimed to assess lung function abnormalities in Lausanne, Switzerland, and their association with clinical history., Methods: In a general population sample, spirometry was performed and bronchodilation applied if the ratio forced expiratory volume in 1 s (FEV1) / forced vital capacity (FVC) or the FVC was below the lower limit of normal (LLN) according to Global Lung Function Initiative 2012 references. Results for FEV1/FVC according to the LLN were compared to the 0.7 fixed ratio. Respiratory risk factors, symptoms and self-reported respiratory diagnoses were recorded through a questionnaire., Results: Out of the 3342 included subjects, 3.8% had chronic obstruction and 2.5% reversible obstruction when using the LLN; possible lung restriction alone was present in 1.8%, and associated with chronic obstruction in 0.4%. Ever smokers had a higher prevalence of abnormal spirometry, chronic obstruction and reversible obstruction; there was no difference with regard to possible restriction. Overall, chronic airway obstruction was found in 8.9% of current smokers, 4.6% of former smokers and 1.5% of never smokers. Only one third of participants with chronic obstruction were aware of a respiratory disease., Conclusion: Prevalence of abnormal lung function in the population of Lausanne is low. This may be due to a low rate of ever-smokers, the application of a full bronchodilation dose, but also to inherent characteristics of this population.

An obstructive ventilatory defect (OVD) is defined by a low forced expiratory volume/'forced/slow' vital capacity (FEV 1 /FVC) (e.g. 1 /FVC < LLN (=local norms value - 1.64 × residual standard deviation)] and GLI (FEV 1 /FVC Z-score < -1.64) criteria. The following OVD classifications severity were applied: ATS/ERS (FEV 1 %pred): mild (>70%), moderate (60-69%), moderately severe (50-59%), severe (35-49%), and very severe (<35%) and GLI (FEV 1 Z-score): mild (≥ -2.0), moderate (-2.0 to -2.5), moderately severe (-2.5 to -3.0), severe (-3.0 to -4.0), and very severe (<-4.0). The frequencies of OVD were 14.4% (ATS/ERS method) and 10.5% (GLI method) (p < 0.05). Among the 103 participants having an OVD according to the two methods, the severity classification was mild (34.95% vs. 37.86%, p < 0.05), moderate (25.24% vs. 18.45%, p < 0.05), moderately severe (23.30% vs. 15.53%, p = 0.144), severe (9.71% vs. 20.39%, p < 0.05), and very severe (6.80% vs. 7.77%, p = 0.785), respectively for the ATS/ERS and GLI classifications. The two OVD definitions were not exchangeable. Moreover, the two grading severity systems misclassified the OVD grades.

We have developed a computational model of gas mixing and ventilation in the human lung represented as a bifurcating network. We have simulated multiple-breath washout (MBW), a clinical test for measuring ventilation heterogeneity (VH) in patients with obstructive lung conditions. By applying airway constrictions inter-regionally, we have predicted the response of MBW indices to obstructions and found that they detect a narrow range of severe constrictions that reduce airway radius to 10%-30% of healthy values. These results help to explain the success of the MBW test to distinguish obstructive lung conditions from healthy controls. Further, we have used a perturbative approach to account for intra-regional airway heterogeneity that avoids modelling each airway individually. We have found, for random airway heterogeneity, that the variance in MBW indices is greater when indices are already elevated due to constrictions. By quantifying this effect, we have shown that variability in lung structure and mechanical properties alone can lead to clinically significant variability in MBW indices (specifically the Lung Clearance Index-LCI, and the gradient of phase-III slopes-Scond), but only in cases simulating obstructive lung conditions. This method is a computationally efficient way to probe the lung's sensitivity to structural changes, and to quantify uncertainty in predictions due to random variations in lung mechanical and structural properties., Competing Interests: The authors have declared that no competing interests exist.

A spectrum of intrapulmonary airway diseases, for example, cigarette smoke-induced bronchitis, cystic fibrosis, primary ciliary dyskinesia, and non-cystic fibrosis bronchiectasis, can be categorized as "mucoobstructive" airway diseases. A common theme for these diseases appears to be the failure to properly regulate mucus concentration, producing mucus hyperconcentration that slows mucus transport and, importantly, generates plaque/plug adhesion to airway surfaces. These mucus plaques/plugs generate long diffusion distances for oxygen, producing hypoxic niches within adherent airway mucus and subjacent epithelia. Data suggest that concentrated mucus plaques/plugs are proinflammatory, in part mediated by release of IL-1α from hypoxic cells. The infectious component of mucoobstructive diseases may be initiated by anaerobic bacteria that proliferate within the nutrient-rich hypoxic mucus environment. Anaerobes ultimately may condition mucus to provide the environment for a succession to classic airway pathogens, including Staphylococcus aureus, Haemophilus influenzae, and ultimately Pseudomonas aeruginosa. Novel therapies to treat mucoobstructive diseases focus on restoring mucus concentration. Strategies to rehydrate mucus range from the inhalation of osmotically active solutes, designed to draw water into airway surfaces, to strategies designed to manipulate the relative rates of sodium absorption versus chloride secretion to endogenously restore epithelial hydration. Similarly, strategies designed to reduce the mucin burden in the airways, either by reducing mucin production/secretion or by clearing accumulated mucus (e.g., reducing agents), are under development. Thus, the new insights into a unifying process, that is, mucus hyperconcentration, that drives a significant component of the pathogenesis of mucoobstructive diseases promise multiple new therapeutic strategies to aid patients with this syndrome.

Background: The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of patients with possible sarcoidosis., Methods: Biopsy-confirmed patients with sarcoidosis seen during a 7-month period at the University of Cincinnati sarcoidosis clinic were prospectively identified. Patients with nonsarcoidosis seen at the same clinic were used as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for presence of biopsy, ≥1 highly probable symptom, and ≥1 at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy)., Results: The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 with biopsy-confirmed sarcoidosis, 150 control patients) to establish cutoff values for SDS biopsy and an SDS clinical and a validation cohort of 380 patients (103 biopsy-confirmed patients with sarcoidosis and 277 control patients). The best cutoff value for SDS biopsy was ≥ 6 (sensitivity, 99.3%; specificity, 100%). For the total the 980 patients, an SDS clinical ≥ 3 had a sensitivity of 90.6%, specificity of 88.5%, and a likelihood ratio of 7.9. An SDS clinical score ≥ 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%)., Conclusions: For sarcoidosis, the presence of specific clinical features, especially multiorgan involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Asthma, chronic rhinosinusitis, and related incurable allergic afflictions of the upper and lower airways are medically important because of their association with the disabling symptom of dyspnea and, at least for asthma, the potential to cause fatal asphyxiation. Extensive research over the past two decades has uncovered both the physiological basis of airway obstruction in asthma and key governing molecular pathways. Exaggerated airway constriction in response to diverse provocative stimuli, termed airway hyperresponsiveness, is mediated through the cytokines interleukin 4 (IL-4) and IL-13 and the transcription factor signal transducer and activator of transcription 6 (STAT6). Overproduction of mucus has long been known to be an essential second component of airway obstruction and is also mediated in part through the IL-4/IL-13/STAT6 pathway. In this review, we discuss a second major signaling pathway which underlies mucus production that is mediated through proteinase-cleaved fibrinogen signaling through Toll-like receptor 4. Unexpectedly, our analysis of human sputum and paranasal sinus fluid indicates that in most cases of severe allergic airway disease, a unique type of airway fungal infection, termed airway mycosis, is pathogenically linked to these conditions. We further discuss how fungal and endogenous proteinases mediate the fibrinogenolysis that is essential to both Toll-like receptor 4 signaling and fibrin deposition that, together with mucus, contribute to airway obstruction.

Objectives: Spirometric evaluation of upper airway obstruction (UAO) is not commonly performed by Otolaryngologists. In addition, functional evaluation of UAO by flow-volume loops (FVL) is not available in all clinical settings. More recently, peak inspiratory flow (PIF) has proven to be a useful tool to monitor UAO at the patient's bedside. The aim of this work is to assess the role of PIF measured with a simple flow metre (In-Check method) as a standardised, simple, non-invasive tool in quantifying chronic and subacute UAO in a routine clinical practice. In addition, a Clinical COPD Questionnaire (CCQ), previously validated to assess the psychophysical status in patients with laryngotracheal stenosis, was utilised to evaluate respiratory function in UAO., Design: Prospective cohort study., Settings: University teaching hospital., Participants: Seventy 2 subjects, an UAO group of 26 patients and a control group of 46 healthy subjects., Main Outcome Measures: The ability of PIF values to discriminate between the UAO group and the control group was assessed using a ROC curve. A Spearman rank correlation was used to test the relationship between PIF measurements and the global CCQ score. Additionally, an analysis of CCQ at domain and items levels was performed., Results: Peak inspiratory flow values were accurate, with an area under the ROC curve (AUC) of 0.98 (P < .05) for differentiating the control group from the UAO group. A threshold PIF value of 170 L/min was found for diagnosing UAO. An inconclusive negative trend was found (r = -.19; P = .35) between PIF values and CCQ global score. Concerning CCQ, the symptoms domain was the most affected by UAO, higher than mental domains (P < .001) as well as functional domains (P < .01). Exertional dyspnoea and cough were the items that obtained the highest disturbed scores., Conclusions: Peak inspiratory flow is a non-invasive, quantitative parameter to evaluate the severity of UAO. Testing can be easily performed in a routine clinical setting, with a non-expensive hand-held device, and could help medical follow-up programmes and prevent emergency situations. However, FVL may be necessary for further assessment of UAO diseases. The CCQ confirms that exertional dyspnoea is the main symptom of UAO, but cough remains a common symptom., (© 2018 John Wiley & Sons Ltd.)

Airflow obstruction is associated with increased cardiovascular morbidity and mortality. However, the causal mechanisms linking airflow obstruction with higher incidence of cardiovascular events remain elusive. We evaluated the relationship between airflow obstruction, a key feature of chronic obstructive pulmonary disease (COPD), and prevalence, extent, and severity of coronary atherosclerosis in a large cohort of asymptomatic subjects. Participants were recruited from those undergoing spirometry and coronary computed tomography angiography (CCTA) as part of a general health evaluation from March 2009 to February 2011. Subjects were required to be over 40 years of age with no known CAD. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%. Obstructive CAD, as measured by CCTA, was defined as maximum intra-luminal stenosis ≥ 50%. Participants with airflow obstruction or normal lung function were compared in terms of obstructive CAD prevalence, the extent and severity of coronary atherosclerosis; including coronary artery calcium score (CACS), atheroma burden score (ABS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS). A total of 1888 subjects were eligible for study inclusion. Compared with participants with normal lung function, those exhibiting airflow obstruction were more likely to have obstructive CAD (p = 0.002). Airflow obstruction was associated with higher CACS (p = 0.043), ABS (p = 0.002), ABOS (p = 0.017), SIS (p = 0.003), and SSS (p = 0.002). Multivariable analyses adjusted for conventional cardiovascular risk factors revealed that airflow obstruction was independently associated with presence of CAD (odds ratio 1.673, confidence intervals [CI] 1.002-2.789, p = 0.048). In this asymptomatic population, the presence of airflow obstruction was associated with a greater prevalence, extent, and severity of coronary atherosclerosis and was seen to be an independent predictor of the presence of CAD.

Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases, both in the clinic and in the development of new respiratory medicines. This article reviews the main challenge agents that are in use today (methacholine, mannitol, adenosine, allergens, endotoxin) and emphasises the importance of controlling how these agents are administered. There is a danger that the optimal value of these challenge agents may not be realised due to suboptimal inhaled delivery; thus considerations for effective and reproducible challenge delivery are provided. This article seeks to increase awareness of the importance of precise delivery of inhaled agents used to challenge the airways for diagnosis and research, and is intended as a stepping stone towards much-needed standardisation and harmonisation in the administration of inhaled airway challenge agents., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose of Review: The application of artificial intelligence in the diagnosis of obstructive lung diseases is an exciting phenomenon. Artificial intelligence algorithms work by finding patterns in data obtained from diagnostic tests, which can be used to predict clinical outcomes or to detect obstructive phenotypes. The purpose of this review is to describe the latest trends and to discuss the future potential of artificial intelligence in the diagnosis of obstructive lung diseases., Recent Findings: Machine learning has been successfully used in automated interpretation of pulmonary function tests for differential diagnosis of obstructive lung diseases. Deep learning models such as convolutional neural network are state-of-the art for obstructive pattern recognition in computed tomography. Machine learning has also been applied in other diagnostic approaches such as forced oscillation test, breath analysis, lung sound analysis and telemedicine with promising results in small-scale studies., Summary: Overall, the application of artificial intelligence has produced encouraging results in the diagnosis of obstructive lung diseases. However, large-scale studies are still required to validate current findings and to boost its adoption by the medical community.

Background: The Air-Smart Spirometer is the first portable device accepted by the European Community (EC) that performs spirometric measurements by a turbine mechanism and displays the results on a smartphone or a tablet., Methods: In this multicenter, descriptive and cross-sectional prospective study carried out in 2 hospital centers, we compare FEV1, FVC, FEV1/FVC ratio measured with the Air Smart-Spirometer device and a conventional spirometer, and analyze the ability of this new portable device to detect obstructions. Patients were included for 2 consecutive months. We calculate sensitivity, specificity, positive and negative predictive value (PPV and NPV) and likelihood ratio (LR +, LR-) as well as the Kappa Index to evaluate the concordance between the two devices for the detection of obstruction. The agreement and relation between the values of FEV1 and FVC in absolute value and the FEV1/FVC ratio measured by both devices were analyzed by calculating the intraclass correlation coefficient (ICC) and the Pearson correlation coefficient (r) respectively., Results: 200 patients (100 from each center) were included with a mean age of 57 (± 14) years, 110 were men (55%). Obstruction was detected by conventional spirometry in 73 patients (40.1%). Using a FEV1/FVC ratio smaller than 0.7 to detect obstruction with the Air Smart-Spirometer, the kappa index was 0.88, sensitivity (90.4%), specificity (97.2%), PPV (95.7%), NPV (93.7%), positive likelihood ratio (32.29), and negative likelihood ratio (0.10). The ICC and r between FEV1, FVC, and FEV1 / FVC ratio measured by the Air Smart Spirometer and the conventional spirometer were all higher than 0.94., Conclusion: The Air-Smart Spirometer is a simple and very precise instrument for detecting obstructive airway diseases. It is easy to use, which could make it especially useful non-specialized care and in other areas.

Background: Most patients with restriction have a pulmonary function test (PFT) pattern in which total lung capacity (TLC), FVC, and FEV 1 are reduced to a similar degree. This pattern is called "simple restriction" (SR). In contrast, we commonly observe a pattern in which FVC percent predicted ( pp ) is disproportionately reduced relative to TLC pp . This pattern is termed "complex restriction" (CR), and we attempted to characterize its clinical, radiologic, and physiologic features., Methods: This study reviewed PFT results of patients tested between November 2009 and June 2013 who had restriction (TLC less than the lower limit of normal). SR was defined as TLC pp -FVC pp  ≤ 10%, and CR was stratified into four classes based on TLC pp -FVC pp discrepancy: Class 1 CR, TLC pp -FVC pp > 10% and ≤ 15%; Class 2 CR, TLC pp -FVC pp > 15% and ≤20%; Class 3 CR, TLC pp -FVC pp > 20% and ≤ 25%; and Class 4 CR, TLC pp -FVC pp > 25%. The medical records of 150 randomly selected patients with SR and 50 patients from each CR class were reviewed., Results: Of 39,277 PFTs completed, we identified 4,532 patients (11.5%) with restriction: 2,407 (6.1%) with SR, 1,614 (4.1%) with CR, and 511 (1.3%) with a mixed pattern. Patients with CR were younger, were more often women, and had a higher prevalence of neuromuscular disease, BMI > 40 kg/m 2 or < 18.5 kg/m 2 , diaphragmatic dysfunction, bronchiectasis, CT mosaic attenuation, and pulmonary hypertension (P < .0001, < .0001, < .001, .004, .0008, .002, .008, .009, .053, and .01, respectively) and a lower prevalence of interstitial lung disease (P < .0001)., Conclusions: CR is a common PFT pattern with distinct clinical features. The associated clinical entities share impaired lung emptying (eg, neuromuscular disease, occult obstruction, chest wall limitation). Clinicians should be aware of this novel PFT pattern and how it shapes the differential diagnosis., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Few studies have described the prevalence of and lung function decline among those with a restrictive spirometric pattern (RSP) in low- and middle-income countries., Methods: We analyzed prospective data from 3055 adults recruited across four diverse settings in Peru over a 3-year period. Multivariable logistic regression was used to study the association between the presence of restriction and associated risk factors. Multivariable linear mixed models were used to determine lung function decline., Results: Among 3055 participants, the average age was 55.4 years (SD 12.4); 49% were male. Overall prevalence of RSP was 4.7%, ranging from 2.8% (Lima) to 6.9% (Tumbes). The odds of having RSP were higher among those who lived in a rural environment (OR 2.19, 95%CI 1.43-3.37), had a diagnosis of diabetes (OR 1.94, 95%CI 1.10-3.40) and among women (OR 2.09, 95%CI 1.41-3.09). When adjusting for baseline lung function, adults with RSP had accelerated decline in forced expiratory volume in 1 s (FEV1) compared with non-obstructed, non-restricted individuals., Discussion: RSP is prevalent particularly among women and in individuals living in rural settings of Peru. When adjusted for baseline lung function, participants with RSP had accelerated rates of FEV1 decline. Our findings are consistent with the notion that RSP is an insidious inflammatory condition with deleterious effects of lung function decline.

Background: Obstructive lung disorder (OLD) is known to be associated with cardiovascular disease. However, the impact of restrictive lung disorder (RLD) on cardiovascular mortality has not been fully investigated in the apparently healthy general population., Objectives: To clarify whether RLD is associated with cardiovascular mortality in the general population., Methods and Results: This community-based cohort study included 3247 subjects who participated in an annual health check in Takahata. We performed spirometry in registered subjects and found that 194 (6%) had RLD, 262 (8%) had OLD, and 73 (2%) had RLD and OLD (Mixed). During a 10-year follow-up, there were 210 deaths, including 57 cardiovascular deaths. Cardiovascular mortality of subjects with RLD was significantly higher than that of subjects with normal lung function. Although the subjects with RLD were younger, comprised fewer smokers, and were more likely to be female than those with OLD, cardiovascular mortality of subjects with RLD was comparable to that of subjects with OLD. Subjects with RLD had a higher prevalence of atrial fibrillation (AF) than those with OLD, and the prevalence of AF was increased with advanced severity of RLD. Multivariate Cox proportional hazard analysis revealed that RLD was an independent predictor of cardiovascular death (hazard ratio 2.61, 95% confidence interval, 1.22-5.21) after adjustment for confounders, but OLD was not. The net reclassification improvement and integrated discrimination improvement were significantly increased by the addition of RLD to conventional cardiovascular risk factors., Conclusion: The presence of RLD was associated with cardiovascular mortality in the general population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cigarette smoking results in the accumulation of iron both systemically and locally, in the lung thereby causing imbalance in iron homeostasis. This disruption in iron homeostasis can be associated with oxidative stress and consequent tissue injury. Therefore, in this study, we tested the association between iron homeostasis and airway obstruction by examining a large cohort of smokers and non-smokers for relationships between 1) serum ferritin and iron concentrations and transferrin saturation and 2) forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), and their ratio (FEV 1 /FVC). Data from the National Health and Examination Survey III were analyzed. The study population included persons aged 20 years and above with their following data recorded: race, gender, serum ferritin and iron concentrations, and transferrin saturation; the final sample number was 7,251. In the total population, Pearson correlation coefficients between 1) serum ferritin and iron concentrations and transferrin saturation and 2) FVC and FEV 1 were significantly positive; whereas those between 1) serum ferritin concentrations and transferrin saturation and 2) FEV 1 /FVC were significantly negative. With separate analyses, serum ferritin concentrations demonstrated positive associations with FVC and FEV 1 but an inverse relationship with FEV 1 /FVC in smokers and non-smokers. Serum ferritin levels increased with worsening airway obstruction among smokers, and its highest concentrations were found among those with the lowest values of FEV 1 /FVC ratio (<60%). Comparable to cigarette smokers, serum ferritin concentrations among non-smokers were greatest in those with the lowest FEV 1 /FVC ratio. Furthermore, elevated levels of serum iron and saturation of transferrin also corresponded with decreased FEV 1 /FVC ratio among non-smokers. Thus, we conclude that indices of iron homeostasis are associated with airway obstruction in both smokers and non-smokers., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: In pediatrics, identifying the severity of bronchial obstruction in an early manner is a decisive factor., Objetive: To assess the psychometric properties of the scales for grading the severity of bronchial obstruction in pediatric patients., Population and Method: This was a systematic review of studies on the validity and reliability of scales for grading the severity of bronchial obstruction conducted in infants and children younger than 3 years old. The search was conducted in Medline, WoS, EMBASE, SciELO, and Google Scholar. The correlation coefficient corresponding to each article was included in a random effects model to establish the criterion validity and reliability using the weighted averages of coefficients as per the sample size., Results: A total of 9 articles were included, which accounted for 2699 children; 3 articles had an adequate or excellent methodological quality. Four articles established the concurrent criterion validity considering oxygen saturation, with a weighted correlation coefficient of -0.627 (95% confidence interval [CI]: -0.767 to -0.431, p < 0.001); 2 articles established the convergent criterion validity, with a weighted correlation coefficient of 0.809 (95% CI: 0.721 to 0.871, p < 0.001); 6 articles established the inter-observer reliability, with a weighted correlation coefficient of0.500for kappa and 0.891 for the intraclass correlation coefficient., Conclusion: The assessment of psychometric properties to support the use of scales for grading the construct "severity of bronchial obstruction" showed a moderate to adequate criterion validity. The percentage of agreement among observers in terms of the studied measure (severity of bronchial obstruction) was adequate; however, weaknesses such as the article design should be taken into account since it may affect the internal validity of results.

Rationale: There is evidence suggesting that birth weight may influence lung function in adulthood, but it is unclear whether it might differentially affect restrictive (FVC) and obstructive (FEV 1 /FVC) patterns., Objectives: To summarize evidence available on the association of birth weight, weight at 1 year, and weight gain in the first year of life with FVC and FEV 1 /FVC in adulthood., Methods: We performed a systematic review of the literature by searching MEDLINE, EMBASE, and Web of Science through January 2015. Data were combined using inverse-variance weighted meta-analysis with random effects models and between-study heterogeneity evaluated. We conducted a priori subgroup or sensitivity analyses by age, country wealth, ethnicity, sex, and smoking. We evaluated risk of bias using the Newcastle Ottawa Scale and reporting bias using funnel plots., Results: Eighteen articles were included in the review and 13 in the meta-analyses. Most studies were from high-income countries, and all had a low risk of bias. We found strong evidence of an association of birth weight with adult FVC, a 59.4 ml higher FVC in adulthood per kilogram increase in birth weight (95% confidence interval, 43.3-75.5), with no evidence of heterogeneity. Evidence of an association of birth weight with FEV 1 /FVC was weaker and showed some inconsistency across studies. Only one study investigated weight at 1 year, and another one reported weight gain in the first year., Conclusions: Our meta-analyses show strong and consistent evidence of an association of birth weight with adult FVC, a measure of restrictive impairment, with much weaker evidence for airflow obstruction.

Background: The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function., Methods: Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome., Results: eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively., Conclusions: In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

Alpha-1 antitrypsin (AAT) is the prototypical protease inhibitor from the serine protease inhibitor (serpin) superfamily that protects lung tissue from proteolytic damage by inhibiting neutrophil elastase. Approximately 1 in 2750 to 1 in 4500 individuals have an autosomal codominant condition that leads to a deficiency of circulating AAT. In individuals with AAT deficiency (AATD), AAT is retained in liver cells, which predisposes them to liver disease, and does not reach lung tissues through circulation, where it normally acts as the primary natural regulator of proteolytic activity in the pulmonary tissues, which thus leads to lung disease. Despite being commonly labeled as a rare disease, AATD is one of the most common autosomal genetic disorders and is considered highly underrecognized, with ≤10% of individuals suspected with AATD identified. Screening guidelines have been established, and the diagnosis is easy to confirm when the condition is suspected. Early recognition is key to prevent morbidity and mortality associated with the disease. For this reason, all patients with chronic obstructive pulmonary disease and patients with asthma and fixed obstruction should be tested to exclude the diagnosis of AATD. Augmentation therapy of the deficient protein is available for those with significant lung disease and protein deficiency, and analysis of recent data supported preservation of lung tissue with this treatment. In this review, oriented toward specialists in allergy and immunology, we focused our discussion on the presentation, diagnosis, and treatment of pulmonary symptoms of AATD.

Background: Drug-induced sedation endoscopy (DISE) is a diagnostic procedure which allows evaluation of the collapsibility of the upper airway. According to expert opinion, it is possible to imitate nocturnal collapsibility and perform a realistic investigation of the site of obstruction and vibration. This should enable sufficient and precise therapeutic advice to be given solely on the basis of clinical assessment., Objective: The current publication critically evaluates the present state of development of DISE and its potential indications., Materials and Methods: A PubMed literature research was performed using "sleep" and "endoscopy" or "DISE" as keywords. Relevant publications were evaluated., Results: The present publication provides a historical summary of the available publications and relates these to other methods for examining obstructive sleep apnea. The present state of DISE in terms of drugs applied, grading systems, and validity is evaluated. Indications for DISE are described and critically discussed on the basis of literature data., Conclusion: DISE provides deep insights into the genesis of obstructions of the upper airway and snoring. Although its value for diagnosis and treatment of sleep-disordered breathing could not yet be demonstrated for all non-CPAP (continuous positive airway pressure) therapies, DISE could identify predictive parameters some methods. Further potential indications for DISE might be predictive examinations for mandibular advancement devices and respiration-synchronous neurostimulation of the hypoglossal nerve. DISE will thus remain a valuable diagnostic tool for obstructive sleep apnea and rhonchopathy.

Background: Whether a fixed cutoff or the lower limit of normal of the FEV1/FVC ratio should be used to diagnose bronchial obstruction is still a matter of debate. This issue is particularly important for elderly people., Objectives: We used equations applicable up to 90 years of age to evaluate the mortality of elderly people diagnosed with bronchial obstruction using either a fixed cutoff of 0.7 or the lower limit of normal (LLN)., Methods: Participants in the SaRA (Salute Respiratoria nell'Anziano, Italian for "Respiratory Health in the Elderly") study were grouped as follows: FEV1/FVC ≥0.7 and ≥ LLN (n = 535: F-/L-), FEV1/FVC <0.7 but ≥ LLN (n = 118: F+/L-), and FEV1/FVC <0.7 and < LLN (n = 229: F+/L+). We estimated the mortality risk in the three groups over 15 years of follow-up., Results: The mean age was 73 years (58% men). The hazard ratio (HR) for mortality was 1.427 (95% CI: 1.09-1.868) in the F+/L- group and 2.143 (95% CI: 1.13-1.995) in the F+/L+ group. After adjustment for potential confounders, we found no increased mortality in the F+/L- group (HR: 1.007, 95% CI: 0.755-1.342), while the HR in the F+/L+ group was still sizeable (1.474, 95% CI: 1.136-1.911)., Conclusions: As expected, using a fixed cutoff translates in a larger number of people to be classified as having bronchial obstruction. In our sample the increased mortality in the F+/L- group is due to the confounding effect of age and sex. Our study lends support to the use of LLN in elderly people., (© 2017 S. Karger AG, Basel.)

Background: Chronic obstructive pulmonary disease (COPD) is globally increasing in frequency and is expected to be the third largest cause of death by 2020. Smoking is the main risk factor of developing COPD. In Greenland, more than half of the adult population are daily smokers, and COPD may be common. International guidelines recommend the usage of spirometry as a golden standard for diagnosing COPD. The current number of spirometries performed among patients treated with medication targeting obstructive pulmonary disease in Greenland remains unexplored., Objective: To estimate the prevalence of patients aged 50 years or above treated with medication targeting obstructive pulmonary disease and the extent to which spirometry was performed among them within 2 years., Design: An observational, cross-sectional study based on the review of data obtained from electronic medical records in Greenland was performed. The inclusion criterion was that patients must have been permanent residents aged 50 years or above who had medication targeting obstructive pulmonary disease prescribed within a period of 15 months prior to data extraction. A full review of electronic patient records was done on each of the identified users of medication targeting obstructive pulmonary disease. Information on age, gender, town and spirometry was registered for each patient within the period from October 2013 to October 2015., Results: The prevalence of patients treated with medication targeting obstructive pulmonary disease aged 50 years or above was 7.9%. Of those, 34.8% had spirometry performed within 2 years and 50% had a forced expiratory volume (1 sec)/ forced vital capacity (FEV1/FVC) under 70% indicating obstructive pulmonary disease., Conclusion: The use of medication targeting obstructive pulmonary disease among patients over 50 years old is common in Greenland. About one third of the patients had a spirometry performed within 2 years. To further increase spirometry performance, it is recommended to explore possible barriers in health care professionals' usage of spirometry in different health care settings in Greenland., Competing Interests: and funding There was no conflict of interest throughout the study. The authors have not received any funding or benefits from industry or elsewhere to conduct this study.

Background: Although the ratio of FEV 1 to the vital capacity (VC) is universally accepted as the cornerstone of pulmonary function test (PFT) interpretation, FVC remains in common use. We sought to determine what the differences in PFT interpretation were when the largest measured vital capacity (VC max ) was used instead of the FVC., Methods: We included 12,238 consecutive PFTs obtained for routine clinical care. We interpreted all PFTs first using FVC in the interpretation algorithm and then again using the VC max , obtained either before or after administration of inhaled bronchodilator., Results: Six percent of PFTs had an interpretive change when VC max was used instead of FVC. The most common changes were: new diagnosis of obstruction and exclusion of restriction (previously suggested by low FVC without total lung capacity measured by body plethysmography). A nonspecific pattern occurred in 3% of all PFT interpretations with FVC. One fifth of these 3% produced a new diagnosis of obstruction with VC max . The largest factors predicting a change in PFT interpretation with VC max were a positive bronchodilator response and the administration of a bronchodilator. Larger FVCs decreased the odds of PFT interpretation change. Surprisingly, the increased numbers of PFT tests did not increase odds of PFT interpretation change., Conclusions: Six percent of PFTs have a different interpretation when VC max is used instead of FVC. Evaluating borderline or ambiguous PFTs using the VC max may be informative in diagnosing obstruction and excluding restriction., (Copyright © 2016 by Daedalus Enterprises.)

Objectives: For the purpose of applying a barometric whole-body plethysmography (BWBP) device as a routine clinical tool in client-owned cats, the objective of this study was to evaluate the methodological importance of simultaneous visual inspection (SVI) of graphic tracing., Methods: To investigate the effect of SVI on the results obtained, 50 client-owned cats were included. Breath-by-breath analysis was conducted with BWBP software, and a commonly used rejection setting was chosen for automatic elimination (AE) of non-breath artefactual waveforms, according to tidal volume (TV), inspiratory and expiratory time, and the difference between inspiratory and expiratory volumes. During 10 mins of data recording, SVI for BWBP waveforms was performed to record manually time periods that were free of any artefacts. The two datasets derived from AE alone (AEA method) and AE plus SVI (SVI-AE method) were compared. The inter-observer effect on the process of SVI was evaluated on six cats., Results: There were statistically significant differences (P <0.001) between the AEA and SVI-AE datasets for most BWBP parameters. Bland-Altman analysis of the parameter-enhanced pause (Penh) showed heterogeneous variances, indicating less agreement when the Penh values were large. Intra-individual coefficients of variation of Penh were significantly higher with the AEA method than with the SVI-AE method (61.1% vs 34.7%, respectively; P <0.001). Inter-observer agreement on the SVI process was excellent, and no statistically significant differences between the two observers were found for any BWBP parameters obtained by the SVI-AE method (P >0.05)., Conclusions and Relevance: Visual inspection for BWBP waveforms in real time can reliably identify stable breathing signals in client-owned cats. The obtained results were significantly different when the SVI method was used in addition to AE. In the interpretation of BWBP parameters or comparison of measurements among studies, whether an SVI methodology was applied should be considered., (© The Author(s) 2015.)

Rationale: Individual assessment of airway obstruction in preschool-age children requires sensitive and specific lung function methods with low demand of cooperation. Although the forced oscillation technique (FOT) is feasible in young children, conventional measurements of respiratory impedance (Zrs) have limited diagnostic power in individuals., Objective: To find descriptors of within-breath Zrs that are sensitive indicators of airway obstruction during tidal breathing in children., Methods: Zrs was measured with (i) a standard multifrequency FOT (4-26 Hz) to assess the mean values of resistance and reactance for whole breaths and (ii) a 10 Hz signal to track the within-breath changes. Various Zrs measures obtained in healthy children (n=75) and those with acute wheeze (n=31) were investigated with receiver operator characteristic (ROC) analysis. The cut-off values obtained for airway obstruction were then tested in children with recurrent wheeze (n=20) before and after administration of salbutamol., Results: The largest area under the ROC curve (0.95) was observed for the tidal changes of resistance between the zero-flow values (ΔR). The ΔR cut-off value of 1.42 hPa s/L detected airway obstruction with sensitivity of 92% and specificity of 89% in children with acute wheeze and distinguished children with recurrent wheeze (16/20 above the cut-off value) from healthy children (22/23 below the cut-off value). Furthermore, ΔR significantly decreased after salbutamol in wheezy children but remained unchanged in healthy children., Conclusions: New lung function measure ΔR is able to detect airway obstruction with high sensitivity and specificity and is suitable for use in lung function testing in young children., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)