Lung Function Variables Research Articles

Mexican Hispanics show significant improvement in lung function approximately 1year after having severe COVID-19.

The long-term effects of COVID-19 on lung function are not understood, especially for periods extending beyond 1year after infection. This observational, longitudinal study investigated lung function in Mexican Hispanics who experienced severe COVID-19, focusing on how the length of recovery affects lung function improvements. At a specialized COVID-19 follow-up clinic in Yucatan, Mexico, lung function and symptoms were assessed in patients who had recovered from severe COVID-19. We used z-scores, and Wilcoxon's signed rank test to analyse changes in lung function over time. Lung function was measured twice in 82 patients: the first and second measurements were taken a median of 94 and 362days after COVID-19 diagnosis, respectively. Initially, 61% of patients exhibited at least one of several pulmonary function abnormalities (lower limit of normal = -1.645), which decreased to 22% of patients by 390days post-recovery. Considering day-to-day variability in lung function, 68% of patients showed improvement by the final visit, while 30% had unchanged lung function from the initial assessment. Computed tomography (CT) scans revealed ground-glass opacities in 33% of patients. One year after infection, diffusing capacity of the lungs for carbon monoxide z-scores accounted for 30% of the variation in CT fibrosis scores. There was no significant correlation between the length of recovery and improvement in lung function based on z-scores. In conclusion, 22% of patients who recovered from severe COVID-19 continued to show at least one lung function abnormality 1year after recovery, indicating a prolonged impact of COVID-19 on lung health.

Demographic factors associated with within-individual variability of lung function for adults with cystic fibrosis: A UK registry study

Background: Lung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates has not been quantified.Methods: We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV1 (forced expiratory volume in 1 s) trajectories and FEV1 within-individual variability as a function of sex, age at annual review, diagnosis after first year of life, homozygous F508 genotype and birth cohort.Results: Mean FEV1 decreased with age and lung function variability showed a near-quadratic trend by age. Males showed higher FEV1 mean and variability than females across the whole age range. Earlier diagnosis and homozygous F508 genotype were also associated with higher FEV1 mean and variability. Individuals who died during follow-up showed on average higher lung function variability than those who survived.Conclusions: Key variables known to be linked with mean lung function in cystic fibrosis are also associated with an individual’s lung function variability. This work opens new avenues to understand the role played by lung function variability in disease progression and its utility in predicting key outcomes such as mortality.

Understanding the Added Value of High-Resolution CT Beyond Chest X-Ray in Determining Extent of Physiologic Impairment

BackgroundSarcoidosis staging has primarily relied on the Scadding chest radiographic system, although chest CT is finding increased clinical use. Research QuestionWhether standardized CT assessment provides additional understanding of lung function beyond Scadding stage and demographics is unknown and the focus of this study. Study Design and MethodsWe used the NHLBI study Genomics Research in Alpha-1 Anti-Trypsin Deficiency and Sarcoidosis (GRADS) sarcoidosis cases(N=351) with Scadding stage and Chest CT scans obtained in a standardized manner. One chest radiologist scored all CT scans with a visual scoring system, with a subset read by another chest radiologist. We compared demographic features, Scadding stage and CT findings, and correlation between these measures. Associations between spirometry and DLCO and CT and Scadding stage were determined using regression analysis (N=318). Agreement between readers was evaluated using Cohen’s Kappa. ResultsCT features were inconsistent with Scadding stage in about ∼40% of cases. Most CT features assessed on visual scoring were negatively associated with lung function. Associations persisted for FEV1 and DLCO when adjusting for Scadding stage, although some CT feature associations with FVC became insignificant. Scadding stage was primarily associated with FEV1 and inclusion of CT features reduced significance in association between Scadding and lung function. Multivariable regression modeling to identify radiologic measures explaining lung function included Scadding stage for FEV1 and FEV1/FVC (P<0.05) and marginally for DLCO (P<0.15). Combinations of CT measures accounted for Scadding stage for FVC. Correlations among Scadding and CT features were noted. Agreement between readers was poor to moderate for presence/absence of CT features and poor for degree/location of abnormality. InterpretationCT features explained additional variability in lung function beyond Scadding stage, with some CT features obviating the associations between lung function and Scadding. Whether CT features/phenotypes/endotypes could be useful for managing patients with sarcoidosis needs more study.

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study

BackgroundLimited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment. ObjectiveTo explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β2-agonist (SABA) usage to determine the clinical relevance of moderate events. MethodsCAPTAIN was a Phase IIIA 24–52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β2-agonist. Outcomes reportedinclude: first post-randomization exacerbation event by severity (Weeks 1–52), frequency and duration of moderate and severe exacerbations and time course of changes over ±14-day peri-exacerbation period for lung function, symptoms, limitations, and SABA use. ResultsOf the intent-to-treat population (N=2436), 550 patients (23%) continued to 52 weeks. There were 529 moderate and 546 severe exacerbations. Lung function changes were similar, but symptom, physical activity limitation scores, and SABA use were higher, for severe versus moderate exacerbations. Lung function decline preceded increases in symptom, physical activity limitation scores, and SABA use, irrespective of exacerbation severity. Lung function variables, limitation scores, and SABA use returned to pre-exacerbation baseline after ∼8–12 days for both exacerbation severities. ConclusionWhile severe events were associated with greater impact on symptoms, physical activity limitations, and SABA use, onset and time to resolution were generally similar for moderate and severe events. Both exacerbation severities represent clinically important deteriorations comprising clinical and functional changes. NCT02924688.

Assessment of lung function variability documents airflow limitation in many patients with long covid

BackgroundIt is estimated that 65 million people worldwide suffer from long covid (LC). Many LC symptoms are also reported by patients with airflow limitation, used to confirm asthma. The primary aim was to detect airflow limitation in LC patients by a methacholine bronchial provocation test (BPT) and if negative, by evaluation of diurnal variability in forced expiratory flow in 1 second (FEV1) over a two-weeks’ period. The second aim was to assess responsiveness to asthma treatment on diurnal FEV1 variability and LC symptoms. MethodsPatients with LC for at least six months were recruited in this open diagnostic study. Burden of LC symptoms were reported on a 10-point Likert scale (0 = not troubled, 10 = extremely troubled) at inclusion and after three weeks’ asthma treatment. A positive methacholine BPT was defined by an accumulated provocation dose (PD20)<8 μmol causing 20% fall in FEV1. App-based spirometer was used for diurnal FEV1 variability, deemed positive by diurnalvariability in FEV1 ≥12%. ResultsAirflow limitation was documented by positive methacholine BPT in 8/30 (27%), or by excessive diurnal variability in FEV1 in 21/22 (95%) of the BPT negative LC patients. One patient dropped out due to personal issues. Three weeks’ asthma treatment normalised mean diurnal FEV1 variability from 18.0% to 7.3%, p < 0.001. Significant reductions were observed for fatigue and dyspnoea, from 8.3 to 6.1, p < 0.001, and 3.0 to 0, p < 0.001, respectively. ConclusionThis study indicate that airflow limitation may be detected in many LC patients if evaluation of diurnal variability in FEV1 is included in the diagnostics.

Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood.

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV1), were measured. (3) Results: FEV1 was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV1 had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV1 was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood.

Circadian rhythm and variability of large and small airway spirometric variables in healthy individuals.

To assess the diurnal rhythm and variability of lung function in healthy individuals, encompassing both large and small airways. A prospective study enrolled 35 healthy adults without a history of smoking. Initial spirometry and a bronchodilation test were performed using the Jaeger spirometer, followed by a seven-day continuous home monitoring using the GOSPT2000. We evaluated repeatability using the intraclass correlation coefficient and agreement through linear regression and Bland-Altman analyses. Circadian rhythm and variability in spirometric measurements were analyzed using the coefficient of variation (CV) and daily variation rate. The GOSPT2000 demonstrated strong repeatability and high agreement with the Jaeger spirometer. Notable findings included a decrease in nocturnal forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV3 by 44, 59, and 53 mL, respectively. In contrast, peak expiratory flow at noon showed an increase of 0.143L/min. Small-airway variables, including forced expiratory flow at 50% and 75% of the FVC and maximum midexpiratory flow, showed no significant diurnal variation. The nocturnal CV for large-airway variables was ≤ 4%, while for small-airway variables, it was ≤ 11.89%. This study has established a spectrum of variability for both large and small airways in healthy populations. The variability of small-airway variables is higher than that of large-airway variables. The investigation into the diurnal rhythms and variability characteristics of both large and small airway variables in the healthy population can serve as a foundation for diagnosing asthma or assessing the efficacy of asthma treatments.

Molecular-genetic foundations of energy exchange and physical qualities of man. Research perspectives

Human physical qualities represent a complex trait influenced by environmental and genetic factors, with most traits being polygenic in nature. The study of the relationship between molecular genetic data, physical characteristics and metabolic individuality (regulation of biogenesis, energy balance, lipid metabolism, glucose homeostasis, etc.) is a promising vector of research, both in the population as a whole and in various nosologies, primarily for hereditary and metabolic diseases characterized by impaired physical development and metabolic balance, including cystic fibrosis (CF), obesity, diabetes mellitus. The first studies were devoted to the study of these parameters in athletes. The genotype-phenotype study in CF has been actively studied for the past few years. It has been shown that environmental factors can determine clinical polymorphism in CF, which account for nearly 50% of lung function variability in this disease. However, CF patients with similar molecular genetic variants of the CFTR gene and in a single habitat (for example, in siblings) can have highly variable clinical manifestations. Genes whose products provide cell energy exchange (PPARA, PPARG, PPARD, PGC-1, UCP2, UCP3, ACTN, ACE) can also be “modifiers” and have an effect on the phenotype, the difference in clinical manifestations of the disease of patients with CF, the relationship of which in this category of patients has not been studied. The world has seen a steady increase in obesity and its complications. Patients with CF from the category of persons with nutritional deficiency in recent decades began to move into the category of overweight patients, which requires study. This review summarizes the recent achievements of studying genes whose products provide energy exchange of the cell, discusses the development of the relationship both with the physical characteristics of individuals and with pathological changes in the body as a result of the appearance of metabolic products in excess or with altered physicochemical properties and functional activity parameters leading to various diseases.

Respiratory impairments in patients suffering from Fabry disease - A cross-sectional study.

The inherited X-linked disorder, Fabry disease, is caused by deficient lysosomal enzyme α-galactosidase A, with progressive accumulation of globotriaosylceramide in multiple organs including the upper and lower airways. To assess pulmonary function at the time of the first pulmonary function test (PFT) performed among the National Danish Fabry cohort and define the prevalence of affected lung function variables. A cross-sectional retrospective cohort study of 86 adult patients enrolled in one or both international patient registry databases for Fabry disease, Fabry Registry or FollowME with at least one PFT. The Mainz Severity Score Index (MSSI) was calculated to determine the disease severity. Lung function variables were examined by multivariate regression adjusted for important variables for developing airway illness. Seventeen patients (20%) showed obstructive airflow limitation and 7 (8%) a restrictive lung deficiency. Smoking status (p = .016) and MSSI (p < .001) were associated with increasing obstructive airway limitation. The prevalence of affected lung function among the National Danish Fabry cohort was 28%. Patients with classic gene variants frequently developed a decrease in lung function regardless of their smoking status, with significant relationship with disease severity.

A Multicenter Study of COPD and Cognitive Impairment: Unraveling the Interplay of Quantitative CT, Lung Function, HIF-1α, and Clinical Variables.

The exact link between cognitive impairment (CI) and chronic obstructive pulmonary disease (COPD) is still limited. Thus, we aim to find the relationship and interaction of quantitative CT (QCT), lung function, HIF-1α, and clinical factors with the development of CI among COPD patients. A cross-sectional multicentre study was conducted from January 2022 to December 2023. We collected clinical data, spirometry, CT images, and venous blood samples from 114 COPD participants. Cognitive impairment assessment using the Montreal Cognitive Assessment Indonesian version (MoCA-Ina) with a cutoff value 26. The QCT analysis consists of lung density, airway wall thickness, pulmonary artery-to-aorta ratio (PA:A), and pectoralis muscles using 3D Slicer software. Serum HIF-1α analysis was performed using ELISA. We found significant differences between %LAA-950, age, COPD duration, BMI, FEV1 pp, and FEV1/FVC among GOLD grades I-IV. Only education duration was found to correlate with CI (r = 0.40; p < 0.001). We found no significant difference in HIF-1α among GOLD grades (p = 0.149) and no correlation between HIF-1α and CI (p = 0.105). From multiple linear regression, we observed that the MoCA-Ina score was influenced mainly by %LAA-950 (p = 0.02) and education duration (p = 0.01). The path analysis model showed both %LAA and education duration directly and indirectly through FEV1 pp contributing to CI. We conclude that the utilization of QCT parameters is beneficial as it can identify abnormalities and contribute to the development of CI, indicating its potential utility in clinical decision-making. The MoCA-Ina score in COPD is mainly affected by %LAA-950 and education duration. Contrary to expectations, this study concludes that HIF-1α does not affect CI among COPD patients.

Capnodynamic end-expiratory lung volume assessment in anesthetized healthy children.

Capnodynamic lung function monitoring generates variables that may be useful for pediatric perioperative ventilation. Establish normal values for end-expiratory lung volume CO2 in healthy children undergoing anesthesia and to compare these values to previously published values obtained with alternative end-expiratory lung volume methods. The secondary aim was to investigate the ability of end-expiratory lung volume CO2 to react to positive end-expiratory pressure-induced changes in end-expiratory lung volume. In addition, normal values for associated volumetric capnography lung function variables were examined. Fifteen pediatric patients with healthy lungs (median age 8 months, range 1-36 months) undergoing general anesthesia were examined before start of surgery. Tested variables were recorded at baseline positive end-expiratory pressure 3 cmH2 O, 1 and 3 min after positive end-expiratory pressure 10 cmH2 O and 3 min after returning to baseline positive end-expiratory pressure 3 cmH2 O. Baseline end-expiratory lung volume CO2 was 32 mL kg-1 (95% CI 29-34 mL kg-1 ) which increased to 39 mL kg-1 (95% CI 35-43 mL kg-1 , p < .0001) and 37 mL kg-1 (95% CI 34-41 mL kg-1 , p = .0003) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively. End-expiratory lung volume CO2 returned to baseline, 33 mL kg-1 (95% CI 29-37 mL kg-1 , p = .72) 3 min after re-establishing positive end-expiratory pressure 3 cmH2 O. Airway dead space increased from 1.1 mL kg-1 (95% CI 0.9-1.4 mL kg-1 ) to 1.4 (95% CI 1.1-1.8 mL kg-1 , p = .003) and 1.5 (95% CI 1.1-1.8 mL kg-1 , p < .0001) 1 and 3 min after positive end-expiratory pressure 10 cmH2 O, respectively, and 1.2 mL kg-1 (95% CI 0.9-1.4 mL kg-1 , p = .08) after 3 min of positive end-expiratory pressure 3 cmH2 O. Additional volumetric capnography and lung function variables showed no major changes in response to positive end-expiratory pressure variations. Capnodynamic noninvasive and continuous end-expiratory lung volume CO2 values assessed during anesthesia in children were in close agreement with previously reported end-expiratory lung volume values generated by alternative methods. Furthermore, positive end-expiratory pressure changes resulted in physiologically expected end-expiratory lung volume CO2 responses in a timely manner, suggesting that it can be used to trend end-expiratory lung volume changes during anesthesia.

Lung function is related to salivary cytokines and hormones in healthy children. An exploratory cross‐sectional study

AbstractPulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z‐score or percent predicted. Ninety‐six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in boys were associated with zR5‐R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM‐CSF. This endogenous influence is a novel concept that warrants in‐depth characterization.

Effects of low workload respiratory training with steam inhalation on lung function in stable asthma: A controlled clinical study.

To investigate effects of low workload respiratory muscle training (RMT) on respiratory muscle power and lung function in asthmatics, we recruited asthmatic persons who performed a 4-week training programme. The training included 20 daily ex- and inhalations with counter pressure 30% from the individual maximal expiratory pressure (MEP). Lung function was measured before and after the training programme and a follow-up period. The study also included several subjective endpoints for respiratory symptoms. A significant increase in a training group (n = 27) compared with a control group (n = 20) was seen in MEP (+12.4%, vs. +3.5%, p = 0.086), maximal inspiratory pressure (MIP) (+21.1% vs. +0.82%, p = 0.023), slow vital capacity (VC) (+3.7% vs. +1.5%, p = 0.023)and in forced expiratory time (FET, +15.5%, vs. -5.0%, p = 0.022). After being a control for group A, also group B performed similar RMT as group A. In the combined group (A and B, n = 47) MEP (11.3%, p = 0.003), MIP (19.73%, p < 0.001), VC (4.1%, p < 0.001)and FET (14.7%, p < 0.001) increased significantly from the baseline. Changes in other lung function variables were not indicative. On a scale of 1-5, the subjects perceived improvement in reduction of mucus secretion in the airways (median 3, p < 0.001), alleviation of coughing (median 3, p < 0.001)and reduction in dyspnoea (median 3, p < 0.001). As a conclusion, low workload respiratory training of 4 weeks improved respiratory muscle power and increased VC in patients with stable asthma.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Use and misuse of random forest variable importance metrics in medicine: demonstrations through incident stroke prediction

BackgroundMachine learning tools such as random forests provide important opportunities for modeling large, complex modern data generated in medicine. Unfortunately, when it comes to understanding why machine learning models are predictive, applied research continues to rely on ‘out of bag’ (OOB) variable importance metrics (VIMPs) that are known to have considerable shortcomings within the statistics community. After explaining the limitations of OOB VIMPs – including bias towards correlated features and limited interpretability – we describe a modern approach called ‘knockoff VIMPs’ and explain its advantages.MethodsWe first evaluate current VIMP practices through an in-depth literature review of 50 recent random forest manuscripts. Next, we recommend organized and interpretable strategies for analysis with knockoff VIMPs, including computing them for groups of features and considering multiple model performance metrics. To demonstrate methods, we develop a random forest to predict 5-year incident stroke in the Sleep Heart Health Study and compare results based on OOB and knockoff VIMPs.ResultsNearly all papers in the literature review contained substantial limitations in their use of VIMPs. In our demonstration, using OOB VIMPs for individual variables suggested two highly correlated lung function variables (forced expiratory volume, forced vital capacity) as the best predictors of incident stroke, followed by age and height. Using an organized analytic approach that considered knockoff VIMPs of both groups of features and individual features, the largest contributions to model sensitivity were medications (especially cardiovascular) and measured medical risk factors, while the largest contributions to model specificity were age, diastolic blood pressure, self-reported medical risk factors, polysomnography features, and pack-years of smoking. Thus, we reach very different conclusions about stroke risk factors using OOB VIMPs versus knockoff VIMPs.ConclusionsThe near-ubiquitous reliance on OOB VIMPs may provide misleading results for researchers who use such methods to guide their research. Given the rapid pace of scientific inquiry using machine learning, it is essential to bring modern knockoff VIMPs that are interpretable and unbiased into widespread applied practice to steer researchers using random forest machine learning toward more meaningful results.

Does avian antigen-induced chronic hypersensitivity pneumonitis lead to more severe PH than other causes of the same?

Sir, Chronic hypersensitivity pneumonitis (CHP) is a prominent aetiology of diffuse parenchymal lung disease (DPLD), contributing to over 47% of the inclusions in the ILD-India registry.[1] The diagnosis of CHP is difficult because the pathological description needs lung biopsy that remains mostly undone. The high-resolution computed tomography (HRCT) chest, however, can give some definite clues for the possibility.[2] In our series, the HRCT diagnosis of HP was done by a pulmonologist and a radiologist on an agreement for the probability of HP in their independent interpretation of HRCT chest pictures. The radiologically possible-HP diagnosis was supported by positive IgG precipitin titre for avian antigen by immunoCAP method.[3] A precipitin titre value >30 mg mgA/L was taken as significant.[3] The clinico-radio-serological positivity was further supported by history of exposure to pigeons/birds to build up a nearly definite avian antigen–induced diagnosis of CHP. However, the possible CHP cases from other causes could not be evaluated serologically as the panel with common antigens was not available to us at that point of time. The study did not essentially include subjects with features of CHP without any etiological confirmation and exclude other causes like connective tissue disease associated-interstitial lung disease (CTD-ILD) and sarcoidosis. The latter was done by a thorough clinical exercise (noting the American Rheumatology Association [ARA]) criteria for the common CTDs supported by the relevant serological tests whenever possible in the real-world situation. Sarcoidosis was diagnosed with demonstration of non-ceasing granuloma with exclusion of tuberculosis. All the patients underwent Doppler echo-cardiography by a single dedicated non-invasive cardiologist who looked systematically for evidence of pulmonary hypertension (PH) in addition to other parameters. Furthermore, we looked for the presence of clinical and radiological XRay -posterio-anterior (PA) view (chest X-ray [PA view] and HRCT) features of PH to satisfy the clinico-radio-echocardiographic screening criteria of the institute for the presence of PH.[4] We had 95 cases of suspected HP included in the evaluation from 2018 to 2019. These patients were sub-divided into two groups - CHP caused due to exposure to avian antigen and CHP likely from other possible etiologies. The above two groups were thus compared on the basis of demographic, spirometric, functional health status and echo-cardiographic variables [Table 1].Table 1: Demographic, spirometric, and functional health status and echocardiographic parameters between the two groups of chronic hypersensitivity pneumonitis (CHP) patientsThe results reflect that the two groups were similar on demographical and spirometric lung function variables, but the patients with CHP from avian antigen had significantly higher systolic pulmonary artery pressure (PAP). To appreciate the relative contribution of the variables for the difference between the two groups, we used the VIP plot that suggested the presence of PAP as the most effective discriminant between the two groups [Figure 1a]. However, the overlap between the clusters was very high, suggesting limited applicability of the information [Figure 1b]. In one of our previous observations, we found a very high frequency HRCT-chest that suggested PH in CHP patients induced by chronic exposure to avian antigen.[4] Such exposure of avian antigen has been found to be one of the common causes of CHP. Avian exposure was present in 21.4% of 513 HP patients in the ILD-India registry,[1] with the adjusted odds ratio of 3.52 (P < 0.001) for developing HP after exposure.[2] Pulmonary hypertension is found quite frequently in CHP[5] and is associated with poor survival prospect.[5] The subjects having CHP with history of exposure to avian antigen had a lesser but statistically insignificant mean duration of illness compared to the other group. The standard deviation in both the groups was very wide for the illness duration, making it unsuitable for interpretation through VIP plot [Figure 2]. Despite the weakness of having no biopsy-proven diagnosis of HP, a non-stringent exclusion of other aetiologies, non-inclusion of treatment history, and dearth of haemodynamic confirmation by right heart catheterisation, our observation demands attention. Furthermore, objective validation of our observation is, thus, warranted.Figure 1: (a) The VIP plot with the variables represents the relative contribution of the parameters to the variance between the study groups, (b) 2D score scatter plot of principal component analysis (PCA) to distinguish the two study groups [avian exposure related and other causes of CHP (chronic hypersensitivity pneumonitis)]showing a significant overlapFigure 2: Comparison of the disease duration between the two study groups [avian exposure related and other causes of CHP (chronic hypersensitivity pneumonitis)]Financial support and sponsorship The research was funded by the organization itself. Conflicts of interest There are no conflicts of interest.

Does BMI Modify the Association between Vitamin D and Pulmonary Function in Children of the Mild Asthma Phenotype?

Vitamin D deficiency and obesity are global health problems that are associated with increased asthma risk in children. The purpose of this study was to investigate whether BMI modifies pulmonary function across vitamin D tertiles in pediatric asthma patients of the mild asthma phenotype. This cross-sectional study conducted from November 2016-September 2017 compared lung function variability as assessed by spirometry and nitric oxide in exhaled breath (FeNO) among 35 normal-weight and 26 overweight/obese Greek schoolchildren (5-12 years old) with mild asthma. Serum 25 (OH)D levels ≥ 30 ng/mL were defined as 'sufficient', 20-30 ng/mL 'insufficient', and &lt;20 ng/mL 'deficient'. Stratification by BMI category, linear regression showed positive associations between D, % FVC (β = 0.49, 95%CI: 0.05, 0.94), and % FEV1 (β = 0.48, 95%CI: -0.01, 0.95) in the normal-weight only, adjusted for age, sex, regular exercise, and medication. FEV1 was 10% higher in the normal-weight D-sufficient group compared to those D-deficient (β = 10.43, 95%CI: 0.54, 20.32). No associations were observed for the overweight/obese group or FeNO. In conclusion, BMI modified associations of vitamin D on airway mechanics in children of the mild asthma phenotype. Serum 25 (OH)D concentrations ≥ 30 ng/mL were associated with higher ventilation in central airways of normal-weight asthmatic children.

Assessment of the adverse effect of crop residue burning on respiratory health: a case study of Patiala, India

BackgroundCrop residue burning (CRB) is one of the top contributors to ambient air pollution (particulate matter 2·5 [PM2·5]) in north-western India. Despite the magnitude of the problems associated with high particulate amounts, there are few epidemiological data in India on the associated health effects of CRB, focusing on rural populations. The present study was conducted to quantify the effect of PM2·5 from CRB on the respiratory health of agricultural community in the Nabha block in Patiala, India. MethodsParticipants aged 10–60 years who were residents of six villages in the Nabha block in Patiala, India, who had resided in the area for at least 10 years and had self-reported as being in good health and non-pregnant women were enrolled in this cross-sectional study using purposive sampling. The participants were recruited from their residence, and all volunteered to participate in the study. The study population was surveyed for self-reported health symptoms and other exposure confounders. Lung function tests (LFTs) were done to examine forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), both during CRB and non-CRB periods. 24-h continuous PM2·5 monitoring was done using the modified low-volume Combo Dust Samplers and particles were collected in glass fiber filters. The PM2·5 mass concentrations were analysed using the standard gravimetric method. Multiple regression models were used to quantify the association of PM2·5 from CRB on respiratory health after controlling for other exposure variables; namely, cooking fuel, ventilation, and distance from the road. FindingsA total of 3644 participants were enrolled from Oct 16 to 26, 2018, and March 7 to April 3, 2019 (the non-CRB periods), and from Oct 27 to Nov 20, 2018 and from Nov 3 to 13, 2019 (CRB periods). The present study showed significant associations between PM2·5 exposure and poor respiratory health with an increased prevalence of respiratory symptoms and lung function decrement among the study population. The older group (>40–60 years) reported more respiratory complaints during CRB than the younger groups (10–18 and >18–40 years), including coughs (OR 1·57; 95% CI 1·14–2·16), phlegm (1·69; 1·19–2·16), and itchiness of the eyes (3·44; 2·54–4·66). The study found a decrease in the results of LFTs with increasing PM2·5 across all age groups during CRB compared with the non-CRB period. The youngest group (10–18 years) had the highest reduction in lung capacity based on LFT variables. In men, FEV1 declined 16% in those aged 10–18 years, 9% in those aged older than 18 to 40 years, and 10% in those older than 40 to 60 years; and in women, it declined 26% in those aged 10–18 years, 12% in those older than 18 to 40 years, and 7% in those older than 40 to 60 years, during CRB (with a mean PM2·5 increase of 167 μg/m3). Similar declines were noted for the other (FVC and PEF) lung function variables. InterpretationThis study, which shows the adverse effects on health from CRB (increases in respiratory symptoms and poor lung function), highlights to need to accelerate policy interventions and engage farmers in discussions on CRB elimination. FundingCentral Pollution Control Board of India (B-33014/40/2018/AQM-EPC 9836).

Cardiopulmonary benefits of respirator intervention against near road ambient particulate matters in healthy young adults: A randomized, blinded, crossover, multi-city study

Wearing a respirator is generally the most convenient individual intervention against ambient particulate matter (PM), and therefore there has been considerable research into its effectiveness. However, the effects of respirator intervention under different PM concentration settings have been insufficiently elucidated. We conducted a randomized, blinded, crossover intervention study in four representative cities in China in which 128 healthy university students spent 2-h walking along a busy road wearing either a real or a sham respirator and then spent the next 5-h indoors away from traffic pollution. Lung function, blood pressure, and heart rate variability were continuously measured throughout the visit. Linear mixed-effect models were fitted to evaluate the protective effects of respirator intervention on the cardiopulmonary indicators. Results showed that the beneficial effects of respirator intervention were only occasionally significant at specific time points or in specific cities or in selected parameters. Overall, respirator intervention was associated with reduced SBP (6.2 vs. 11.5 mmHg compared to baseline, p < 0.05) and increased LF (44 vs. 35 ms2 compared to baseline, p < 0.05) over the 2-h walk, but no significant effects were found over the 7-h period. Respirators have significant effect modifications on the associations between PM2.5/PM10 and the cardiopulmonary indicators, but the directions of effects were inconsistent. The intercity difference in the effects of respirator intervention was found significant, with Taiyuan and Shanghai to be the two cities with lower personal PM concentrations but more pronounced benefits. In conclusion, reducing personal exposure to PM can have some beneficial effects in some scenarios. However, respirators may not provide sufficient protection from air pollution overall, and we should avoid over-reliance on respirators and accelerate efforts to reduce emissions of pollutants in the first place. Despite standardized procedures, we found inconsistency in results across cities, consistent with the previous literature.

To study the role of sputum cytology in patients with bronchial asthma and COPD

COPD is the major cause of morbidity and mortality across the world. In addition to this, the major factor that is contributing in this disease is smoking. This kind of problem occurs due to airflow obstruction that influences the progressive and accompanied hyper-responsiveness. The patients with Asthma and COPD overlap (ACO) have a poor quality of life and more rapid decline in lung functions and high mortality. Also, they consume a disproportionate amount of health care resources. Moreover, sputum cell counts are extensively used in the treatment of asthma and COPD. The clinical application of sputum cell count in patients with both COPD and asthma remain elusive. The study aims to study the role of sputum cytology in patients with Bronchial Asthma and COPD. It was a prospective study carried out in the Department of Pulmonary Medicine, D Y Patil Medical College, Nerul, Navimumbai, Maharashtra, India. The period of the study was from January 2020 to June 2021. The number of healthy patients recruited for the current study was 20, along with 20 asthmatic patients and 30 COPD patients. Spirometry and body plethysmography was used to measure the capacity and volume of the lungs of all the patients. One-Way Analysis of Variance (ANOVA) test was conducted for counting the differences in counts of lung function variables and sputum cells. The mean age of healthy patients was 62.78±6.1 years, asthmatic patient was 55.9±12.8 years and COPD patients was 65.8±5.2 years. According to the analysis, the specific airway's conductance for aesthetic patients was [0.60±0.04 kPa.Sec⁻¹] and for the patient who was suffering from COPD, the score was [1.82±0.19 kPa.Sec⁻¹] and the outcome for healthy patients was [1.19±0.12 kPa.Sec⁻¹].The study has found a strong relationship between sGaw and neutrophil and the neutrophil-macrophage ratio of COPD patients. According to the analysis of the study outcome, eosinophils are important for the respiratory inflammatory infiltrates in asthma patients as well as in COPD.