Abnormal Lung Function Research Articles

Adding Oscillometry and Fractional Exhaled Nitric Oxide to Guidelines Potentially Enhances Identification of Exacerbation Risk Factors in Asthmatic Children

ABSTRACTBackgroundA possible explanation for the continued risk of asthma exacerbations while utilizing current asthma guideline‐based management is the failure to consider small airway dysfunction (SAD) and eosinophilic airway inflammation in assuming asthma‐controlled status.ObjectiveTo construct a practical algorithm that potentially identifies additional risks of not well‐controlled (NWC) asthma and exacerbations beyond guideline criteria with oscillometry and fractional exhaled nitric oxide (FENO) determination.MethodsThis was a retrospective, posthoc analysis of 183 children, ages 4–18 years, with moderate‐to‐severe asthma, characterized by demographic factors, National Health Lung and Blood Institute (NHLBI) determined asthma‐controlled status, therapy step, and lung function status. Impulse oscillometry (IOS) and FENO were performed before spirometry. Abnormal lung function values were determined for spirometry, SAD, and FENO based on established thresholds. Statistical analysis included a decision tree and Venn diagram.ResultsFor 53 patients with guideline‐based NWC, 15 (28.3%) had an FEV1 ≤ 80% predicted. An additional 30 patients (56.6%) had abnormal SAD and/or FENO with a preserved FEV1. Of 130 patients, well‐controlled (WC) by guidelines 76 (58.5%) exhibited SAD and/or abnormal FENO.ConclusionsThese data demonstrate that over 50% of WC patients with moderate‐to‐severe asthma, with few symptoms and preserved FEV1, had SAD and/or abnormal FENO levels, suggesting the potential of early phenotype‐specific therapy to prevent risk of future exacerbations.

Association between humidity and respiratory health: the 2016–2018 Korea National Health and Nutrition Examination Survey

BackgroundAmbient humidity has a significant impact on respiratory health and influences disease and symptoms. However, large-scale studies are required to clarify its specific effects on lung function and respiratory symptoms. We examined the relationship between relative humidity (RH), lung function, and respiratory symptoms using data from the Korea National Health and Nutrition Examination Survey (KNHANES).MethodsIn this cross-sectional study, we analyzed data from KNHANES participants aged ≥ 40 years, collected between 2016 and 2018. Pulmonary function tests (PFTs) and health questionnaires were used to assess lung function and respiratory symptoms. Individual environmental data, including RH, were obtained from the Community Multiscale Air Quality model and linked to the participants’ addresses. Short-term (0–14 days), mid-term (30–180 days), and long-term (1–5 years) RH exposures were examined. Linear regression models were used to evaluate the associations between RH and PFTs. Univariate and multivariable logistic regression models were applied to assess the risk of lung function abnormalities and respiratory symptoms.ResultsIn total, 10,396 participants were included (mean age: 58.3 years, male: 43.6%). In multiple regression analysis, higher RH was negatively associated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio across various time lags, while FVC was positively correlated with long-term RH exposure. In multiple logistic analysis adjusted for clinical and environmental covariates, long-term higher RH exposure was associated with a lower risk of restrictive lung disease (odds ratio [OR] at 4-year moving average [MA]: 0.978, 95% confidence interval [CI]: 0.959–0.997), while mid-term RH exposure decreased the risk of chronic cough (OR at 90-day MA: 0.968, 95% CI: 0.948–0.987) and sputum production (OR at 90-day MA: 0.985, 95% CI: 0.969–1.001).ConclusionsHigher RH was negatively associated with lung function and increased the risk of obstructive lung disease, whereas mid-term RH exposure reduced the risk of chronic cough and sputum production.

Perception of quality of life in school-age children born before 32weeks of gestational age.

In our population of preterm school-aged childrenwith grades 2-3 BPD, worseperceived quality of lifewas reported compared tothose with no BPD or grade 1 BPD. Preterm children who developed asthma symptoms during the follow-up period also reported lowerperceived quality of life. No differences in QoL were observed between patients with no BPD and those with grade 1 BPD, or between thoseborn before and after 28weeks ofgestation.These findings highlightthe importance of assessing the QoLin preterm patients with BPD, particularly those with grade 2-3 BPD or asthma symptoms, as early assessment can help identify patients who may benefit from targeted interventions to improve quality of lifeand long-term outcomes. • Survival rates of extremely preterm infants have increased significantly in recent years, but respiratory morbidity, particularly bronchopulmonary dysplasia, remains a common problem. The impact of BPD on the quality of life of preterm infants, particularly at school age, is still debated. BPD is associated with an increased risk of asthma and abnormal lung function, but its effect on QoL is not fully understood. • Preterm infants with grade 2-3 BPD have a significantly worse perception of QoL at school age, especially in the domain of "social activities". This finding emphasises the need for long-term follow-up and possible interventions to improve QoL, especially in terms of social integration. Asthma symptoms during childhood also contribute to poorer QoL perceptions, highlighting the importance of early diagnosis and effective treatment.

Smoking and outcomes in candidates for Liver Transplantation: Analysis of the pulmonary vascular complications of liver disease 2 (PVCLD2).

Patients with chronic liver disease commonly have abnormal lung function, however the impact of smoking on outcomes in these patients is unknown. We hypothesized current or past smoking would be associated with worse survival in patients with advanced liver disease. The Pulmonary Vascular Complications in Liver Disease Study 2 (PVCLD2) was a prospective cohort of patients with advanced liver disease undergoing evaluation for liver transplantation (LT). Patients were classified by self-report as a "non-smoker", "past smoker", or "current smoker". We used Cox proportional hazards models and Fine-Gray models with LT as a competing risk. Models were adjusted for age, sex, body mass index, race, family income, liver disease etiology, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score. Of the 410 patients included, most (65%) were male with mean age at enrollment was 56.5 years. 160 (39%) patients were non-smokers, 183 (45%) were past smokers, and 67 (16%) were current smokers. In total, 151 (37%) patients received a LT, and 88 (20%) patients died. When compared to non-smokers, current smokers had a 2.17-fold increase in risk of death overall (95% CI 1.12-4.18, p=0.02). There was a 7% increase in overall risk of death for every 5 pack-years increase (95% CI 1.01-1.13, p=0.02). With LT as a competing risk, the sub-distributional hazard ratio (sHR) of current smokers versus non-smokers for death was 2.45 (95% CI 1.31-4.60, p=0.005). In this model, past smokers displayed a non-significant increase in risk of death compared to non-smokers (sHR1.58, 95% CI 0.91-2.72, p=0.10). Patients with advanced liver disease undergoing evaluation for LT who smoke have an increased risk of death. Smoking cessation could lead to improved overall survival with or without LT.

Identification of Post-Tuberculosis Lung Function Impairment Early during the Course of Treatment.

Tuberculosis (TB) is a leading cause of morbidity and mortality and an important contributory factor to chronic lung disease. TB-associated permanent lung damage manifests with varying levels of respiratory disability long after TB has been successfully treated, which is a condition known as post-TB lung disease (PTLD). This study assessed whether lung function impairment associated with PTLD occurs early during TB treatment. Using a cross-sectional design, we enrolled newly diagnosed adult TB patients aged ≥18 years who had received anti-TB medication for ≥2 months from a large treatment center in northern Nigeria. We used spirometry and the Global Lung Initiative 2012 reference equations for African Americans to assess and characterize lung function for enrolled participants (N = 94). The median age (range) of participants was 34 (18-72) years. Approximately 5.3% (n = 5) of participants exhibited features of abnormal lung function, 4.2% (n = 4) showed features of obstructive lung abnormality, and 1.1% (n = 1) showed restrictive lung abnormality. Compared with historical patients recruited ≥6 months after TB treatment in the same center, our participants had significantly lower forced expiratory volume in one second and forced vital capacity values. Our findings suggest an opportunity for early intervention for primary and secondary prevention of PTLD to reduce the impact of severe respiratory impairment.

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor treatment in children aged 6-11 years with cystic fibrosis in a real-world setting.

Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulating therapy for people with CF and at least one F508del variant. However, there is limited data about the safety and efficacy of this therapy in pediatric populations and in real-world settings. This study aimed at evaluating the effectiveness, tolerability, and safety of ETI in children with CF. This was a prospective observational study including all children aged 6-11 years who initiated ETI therapy between October 2022 and March 2023 at the Pediatric CF Center of Milan (Italy). Study outcomes included changes in sweat chloride concentration, FEV1, LCI2.5, body mass index(BMI), tolerance, and safety. Mean changes in study outcomes from baseline through 24 weeks were estimated using mixed-effects regression models. The study included 34 children with CF (median age: 8.3 years). At Week 12, we observed an average decrease in LCI2.5 of 2.3 units (95% confidence interval [CI]: -3.1; -1.5). At Week 24, sweat chloride concentration decreased by 63 mEq/L (95% CI: -69; -58), FEV1 increased by 8.8 percentage point (95% CI: 3.7; 13.9) and BMI increased by 0.15 standard deviation scores (95% CI: 0.04; 0.25). Skin rashes appeared in 6 patients which spontaneously resolved within a few days. One month after treatment initiation, one patient experienced an elevation in liver function test results, which subsequently decreased during follow-up visits without necessitating discontinuation of therapy. Our data indicate that ETI therapy is well tolerated by children with CF and is effective in improving signs of lung function abnormalities from early childhood.

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.

Analysis of factors affecting health status and abnormal lung function of workers exposed to welding fumes in Tianjin from 2020 to 2022

Objective: To investigate the health status and the influencing factors of abnormal lung function of welding fumes exposure workers in Tianjin from 2020 to 2022, and to provide theoretical basis for the protection and intervention of key occupational diseases. Methods: In October 2023, the relevant data of occupational health examination of welding fumes exposure workers in Tianjin from 2020 to 2022 (10831, 10758 and 21717 in 2020, 2021 and 2022, respectively) were collected from the China Disease Prevention and Control Information Platform. The electrocardiogram, chest radiograph and lung function abnormalities of workers in each year were analyzed, as well as the association between lung function abnormalities and gender, age, working age, region, etc. With gender, age and years of service as independent variables, logistic regression analysis was performed year by year on the influencing factors of abnormal lung function. Results: From 2020 to 2022, electrocardiogram, chest radiograph and lung function abnormality rates of workers exposed to welding fumes had statistical significances (χ(2)=301.79, 7.87, 1614.54, P<0.05), and the lung function abnormality rate showed a downward trend year by year (χ(2)(trend)=1516.19, P<0.001). The abnormal rates of lung function in male workers exposed to welding fumes were higher than those in female workers (χ(2)=61.65, 8.04, 15.22, P<0.05). With the increase of age, the abnormal rate of lung function showed an increasing trend (χ(2)(trend)=6.47, 10.81, 4.72, P<0.05). The abnormal rates of lung function in the four districts around the city in each year were 22.05% (318/1442), 8.91% (171/1919) and 6.48% (273/4212), respectively. Year by year logistic regression analysis showed that females were the protective factors for abnormal lung function (OR=0.369, 0.568, 0.546; 95%CI: 0.298-0.458, 0.367-0.879, 0.388-0.767; P<0.05) . Conclusion: Attention should be paid to the health status of welding fumes workers in Tianjin, focusing on the protection of middle-aged male workers, and effective prevention measures should be taken for key areas and industries such as the four districts around the city.

Musculoskeletal, Pulmonary, and Cardiovascular COVID-19 Sequelae in the Context of Firefighter Occupational Health: A Narrative Review.

For most individuals infected with SARS-CoV-2, the acute illness resolves completely. However, for millions of people, symptoms or sequelae from COVID-19 recur or persist for months to years after infection. Post-COVID-19 sequelae are wide-ranging, often affecting the musculoskeletal, pulmonary, and cardiovascular systems. All who experience post-COVID-19 sequelae face significant challenges navigating home and work life. Occupations such as firefighting, however, are of particular concern given the strenuous nature of a job that relies on a healthy musculoskeletal, pulmonary, and cardiovascular system. Research has documented significant musculoskeletal impairment (including muscle weakness, pain, and fatigue), respiratory dysfunction (including reduced lung function, interstitial disease, and diffusion abnormalities), cardiovascular conditions (including cardiac events, ischemic disease, dysrhythmias, and infectious diseases), and diminished cardiorespiratory fitness that continues for months to years in some individuals. These persistent post-COVID-19 conditions may affect a firefighter's ability to return to work, function at full capacity while at work, and potentially compromise firefighter health and public safety. This review, therefore, explores musculoskeletal, pulmonary, and cardiovascular sequelae post-COVID-19 and the impact of these sequelae on firefighter health and occupational readiness.

Impact of polyfluoroalkyl chemicals and volatile organic compounds exposure on lung function of American adults

BackgroundEnvironmental chemicals, such as Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and volatile organic compounds (VOCs), and the association between the combined exposure of these chemicals and human lung function remains unclear. This study aimed to explore the effects of mixed exposure to PFAS and VOCs on lung function in the general population of the United States and investigate their potential mechanisms. MethodsData from 30442 respondents were selected for analysis during the US National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2012. Linear models, weighted quantile (WQS) regression, quantile g calculation (QGC), and Bayesian kernel machine regression (BKMR) were used to evaluate the contribution of individual components. Moreover, the interactions between substances in the dose-response relationship mixture of multiple environmental chemical exposures and lung function were also evaluated. The Benjamini-Hochberg method was used to correct multiple tests. FindingsUnivariate analysis showed that nitromethane was negatively correlated with FEV1 (β =−0.052), FVC (β =−0.056), and PEF (β =−0.065), while perfluorohexanesulfonic acid was positively associated with FEV1 (β = 0.026), FVC (β = 0.024), FEF25-75% (β = 0.012), and PEF (β = 0.029). Multivariate analysis showed that chloroform and perfluorohexane sulfonic acid were positively associated with lung function (P <0.05), and perfluorohexane sulfonic acid contributed the most. Nitromethane and perfluorodecanoic acid were negatively associated with lung function (P < 0.05), and perfluorodecanoic acid contributed the highest weight in the negative direction. When all chemicals were in the 50th percentile, the environmental chemical mixture had no significant consistent effect or dose-response on lung function. There were interactions among various environmental chemicals within the mixture except for 2-N-methyl-PFOSA acetate and bromodichloromethane. InterpretationThese results suggest that environmental mixture exposure is associated with abnormal lung function in American adults, and the interaction of various substances in the mixture affects its physiological and chemical effects.

Comparison of Longitudinal Outcomes in Children with Primary Ciliary Dyskinesia and Cystic Fibrosis.

Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) are both genetic diseases of mucociliary clearance resulting in progressive lung disease with onset in early life. PCD is often considered to be milder in childhood than CF, based on minimal evidence. Similar to CF, genotype-phenotype associations exist in PCD: pathogenic variants in CCDC39 and CCDC40, causing inner dynein arm/microtubular defects (IDA/MTD) are associated with more severe disease. To compare longitudinal outcomes in matched children with PCD and CF. We hypothesized that children with PCD with IDA/MTD defects would have lower lung function but better nutritional indices than matched children with CF with minimal function genotypes (i.e., those associated with pancreatic insufficiency). Children with PCD enrolled in a prospective, multicenter, observational study were matched with CF patients from the CF Foundation Patient Registry by birth cohort, age, sex, race/ethnicity and year of study visit. The association of disease group overall and by severity class (PCD-IDA/MTD versus all other defects and CF-minimal versus residual function) with longitudinal outcomes up to age 17 was evaluated with cubic spline mixed effects models. Groups included 136 children with PCD (40 IDA/MTD, 96 other) and 476 with CF (446 minimal function, 30 residual function). Below age 14, the PCD group had similar or lower estimated mean FEV1 % predicted compared to CF (e.g., at age 10, -5.4 % predicted lower (95% CI: -7.7, -3.1)). Compared to the CF-minimal function (pancreatic insufficient) group, the PCD-IDA/MTD group had similar BMI; estimated mean FEV1 % predicted was significantly lower by age 10 (mean difference -10.6% (95% CI: -14.7, -6.4), increasing to -15.7% (95% CI: -20.3, -11.2) at age 14. The CF cohort had increased prevalence of Pseudomonas aeruginosa cultured on one or more occasions compared to children with PCD (67% vs 27%, p<0.001); there was no difference in prevalence of P. aeruginosa between children with PCD-IDA/MTD and PCD-other. In childhood, average lung function abnormalities in PCD are not milder than CF, particularly for those with IDA/MTD ciliary defects. New guidelines and treatments to improve outcomes in PCD are urgently needed.

Tuberculosis-Associated Respiratory Disability in Children, Adolescents, and Adults: Protocol for a Systematic Review and Individual Participant Data Meta-Analysis.

Approximately 2% of the global population has survived tuberculosis (TB). Increasing evidence indicates that a significant proportion of pulmonary TB survivors develop TB-associated respiratory disability, commonly referred to as post-TB lung disease (PLTD) and marked by impaired respiratory function, persistent symptoms, and activity limitations. However, the prevalence, risk factors, and progression of TB-associated respiratory disability throughout the life course are not well understood. To address these gaps, we will undertake a systematic review and individual participant-level data meta-analysis (IPD-MA) focusing on TB-associated respiratory disability in children, adolescents, and adults successfully treated for pulmonary TB. We will systematically search MEDLINE, Embase, CENTRAL, Global Index Medicus, and medRxiv for original studies investigating TB-associated respiratory disability in people of all ages who have completed treatment for microbiologically confirmed or clinically diagnosed pulmonary TB. Authors of eligible studies will be invited to contribute de-identified data and form a collaborative group. Primary outcomes will be (1) abnormal lung function based on spirometry parameters and (2) chronic respiratory symptoms. We will estimate the overall and subgroup-specific prevalence of each outcome through IPD meta-analysis. Next, we will develop clinical prediction tools assessing the risk of future TB-associated respiratory disability at (i) the start of TB treatment and (ii) end of TB treatment for those without existing signs of disability. Finally, we will use stepwise hierarchical modelling to identify epidemiological determinants of respiratory disability. This study has been approved by the ethics review boards at the Rhode Island Hospital (2138217-2) and the Research Institute of the McGill University Health Centre (2024-10345). Individual study authors will be required to obtain institutional approval prior to sharing data. Results will be disseminated through open-access, peer-reviewed publications and conference presentations. CRD42024529906.

Lung function at 1-year follow-up in patients with persistent dyspnea after mild COVID-19 – comparisons with moderate and critical COVID-19

Aim: To assess lung function in patients with persistent dyspnea 1 year after mild coronavirus disease 2019 (COVID-19) and compare with those hospitalized with moderate or critical COVID-19. Methods: Adults with confirmed severe acute respiratory syndrome coronavirus-2 infection with mild COVID-19 and persistent dyspnea (n = 18) or with moderate (n = 34) or critical COVID-19 (n = 19) were followed up 11–13 months after initial infection. Inclusion criteria were age &lt; 65 years, no smoking history, and no preexisting respiratory diseases. Sociodemographic and clinical data were collected, and patients underwent spirometry and measurement of diffusing capacity for carbon monoxide (DLCO). Results: The non-hospitalized patients were significantly younger and more often female compared with those in the moderate and critical groups (P = 0.002 and P &lt; 0.001, respectively). No significant differences in comorbidities or body mass index (BMI) were noted between severity groups. An obstructive spirometry pattern (ratio of forced expiratory volume during the first exhalation second to forced vital capacity under the lower limit of normal (LLN)) was found in 5.6, 5.9, and 5.3% of patients in the mild, moderate, and critical groups, respectively (P = 0.995). Abnormal DLCO (&lt; LLN) rates were seen in 5.6, 16.7, and 47.4% in the mild, moderate, and critical groups, respectively (P = 0.018). DLCO, expressed as a z-score, was significantly lower in the critical group compared with the mild group after adjustment for age, sex, and BMI. Conclusion: Only a few subjects with mild COVID-19 and persistent dyspnea had abnormal lung function 1 year after initial infection, assessed based on spirometry and DLCO measurements. An obstructive spirometry pattern at 1-year follow-up was uncommon even in patients with moderate or critical COVID-19. Impaired DLCO was more common in patients with critical COVID-19.

Lung function and health-related quality of life among adult patients following pulmonary TB treatment.

<sec><title>OBJECTIVES</title>Pulmonary TB (PTB) increases the risk of chronic lung complications, which are associated with increased morbidity and mortality. We determined the prevalence and predictors of post-TB lung disease and persistent symptoms in a resource-limited setting.</sec><sec><title>METHODS</title>Adults who completed PTB treatment underwent spirometry and completed the St. George's Respiratory Questionnaire (SGRQ), a questionnaire that assesses quality of life on symptom, activity, and impact. We performed multivariate analyses to calculate the X-adjusted prevalence ratio (PRadj) of abnormal spirometry and identify associated risk factors.</sec><sec><title>RESULTS</title>Among the 162 participants, 89 (54.9%) were male. The median age was 32 years, and 65 (40.1%) had HIV. Overall, 65 participants (40.1%) had abnormal lung function, with spirometric restriction seen in 29.0%, obstruction in 4.9%, and a mixed pattern in 6.2%. Smoking (PRadj 1.88, 95% CI 1.11-3.16; P = 0.02) and female sex (PRadj 1.81, 95% Cl 1.15-2.84; P = 0.01) were independent risk factors for abnormal lung function. The median SGRQ scores were higher in participants with cavitation (P < 0.001) or bilateral consolidation on initial chest X-ray (P = 0.01).</sec><sec><title>CONCLUSIONS</title>Lung function abnormalities, particularly spirometric restriction, are common in patients completing PTB treatment. Female sex and smoking status were associated with lung function abnormalities; therefore, additional studies to understand the underlying mechanistic pathways are warranted.</sec>.

Assessing the prevalence and impact of preserved ratio impaired spirometry in low-income and middle-income countries: a post-hoc cross-sectional analysis

More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings. We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV1) of less than 80% predicted with a FEV1/forced vital capacity ratio of 0·70 or more. We used t tests and χ2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs. 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25). The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk. Medical Research Council.

Histological Scoring Systems for the Assessment of the Degree of Lung Injury in Rats

Acute respiratory distress syndrome (ARDS) is a serious pulmonary reaction with well-defined clinical parameters in humans triggered by many causes besides bacterial and viral pneumonia. However, there is no definitive definition of ARDS parameters in the experimental animal model. With its 2010 workshop report, the American Thoracic Society defined the main histopathological features that determine the presence of ARDS in laboratory animals, such as changes in parenchymal tissue, altered integrity of the alveolar capillary barrier, inflammation, and abnormal lung function. Understanding these parameters, scoring tissue lesions is used to convert observational pathological data into semi-quantitative or quantitative data for statistical analysis and improved precision.

Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity?

In the postacute phase of coronavirus disease-2019 (COVID-19), survivors may have persistent symptoms, lung function abnormalities, and sequelae lesions on thoracic computed tomography (CT). This new entity has been defined as post-COVID interstitial lung disease (ILD) or residual disease. To evaluate the characteristics, risk factors and clinical significance of post-COVID ILD. Multicenter cross-sectional analysis of data from a randomized clinical study. In this study, patients with persistent respiratory symptoms 3 months after recovery from COVID-19 were evaluated by two pulmonologists and a radiologist. post-COVID ILD was defined as the presence of respiratory symptoms, hypoxemia, restrictive defect on lung function tests, and interstitial changes on follow-up high-resolution computed tomography (HRCT). At the three-month follow-up, 375 patients with post-COVID-19 syndrome were evaluated, and 262 patients were found to have post-COVID ILD. The most prevalent complaints were dyspnea (n = 238, 90.8%), exercise intolerance (n = 166, 63.4%), fatigue (n = 142, 54.2%), and cough (n = 136, 52%). The mean Medical Research Council dyspnea score was 2.1 ± 0.9, oxygen saturation was 92.2 ± 5.9%, and 6-minute walking distance was 360 ± 140 meters. The mean diffusing capacity of the lung for carbon monoxide was 58 ± 21, and the forced vital capacity was 70% ± 19%. Ground glass opacities and fibrotic bands were the most common findings on thoracic HRCT. Fibrosis-like lesions such as interlobular septal thickening and traction bronchiectasis were observed in 38.3% and 27.9% of the patients, respectively. No honeycomb cysts were observed. Active smoking [odds ratio (OR), 1.96; 95% confidence interval (CI), 1.44-2.67), intensive care unit admission during the acute phase (OR, 1.46; 95% CI, 1.1-1.95), need for high-flow nasal oxygen (OR, 1.55; 95% CI, 1.42-1.9) or non-invasive ventilation (OR, 1.31; 95% CI, 0.8-2.07), and elevated serum lactate dehydrogenase levels (OR, 1.23; 95% CI 1.18-1.28) were associated with the development of post-COVID ILD. At the 6-month follow-up, the respiratory symptoms and pulmonary functions had improved spontaneously without any specific treatment in 35 patients (13.4%). The radiological interstitial lesions had spontaneously regressed in 54 patients (20.6%). The co-existence of respiratory symptoms, radiological parenchymal lesions, and pulmonary functional abnormalities which suggest a restrictive ventilatory defect should be defined as post-COVID-19 ILD. However, the term “fibrosis” should be used carefully. Active smoking, severe COVID-19, and elevated lactate dehydrogenase level are the main risk factors of this condition. These post-COVID functional and radiological changes could disappear over time in 20% of the patients.

PM2.5 exposure and household income are associated with lung function abnormalities in children with sickle cell disease.

Cardiopulmonary dysfunction is a major contributor to mortality among persons with sickle cell disease (pwSCD). Despite this, little is known regarding environmental drivers of lung function decline. We hypothesized that environmental and socioeconomic variables have a significant effect on lung function in pwSCD that can be detected by spirometry. We retrospectively analyzed all spirometry results from pwSCD followed in the Pediatric Pulmonology clinic at the Children's Hospital of Philadelphia since 1 January 2016. The study included 349 spirometry tests from 128 patients, primarily "Black or African American" (88%) and male (61%). More frequent exposure to PM2.5 above 25 μg/m3 was associated with higher odds of obstruction. Specifically, when compared to incidence of exposure to PM2.5 above 25 μg/m3 <25th percentile, both pwSCD exposed to 25th-75th percentile and pwSCD >75th percentile had higher odds of obstruction on spirometry (25th-75th: odds ratio [OR]: 9.6, p = .017; >75th:OR: 31.85, p = .002) despite correction for potential confounders. Similarly, median household income below the mean was associated with higher odds of restriction (OR: 4.37; p = .009). We report higher odds of obstruction in pwSCD frequently exposed to PM2.5 concentrations above 25 μg/m3 and higher odds of restriction in pwSCD with lower household income. Our findings link spirometry patterns to modifiable risk factors indicating that there may opportunities for early intervention in pwSCD that have been referred to a pulmonology clinic. Further research is needed to assess if these findings can be generalized to the wider population of pwSCD.

Identification of factors directly linked to incident chronic obstructive pulmonary disease: A causal graph modeling study.

Beyond exposure to cigarette smoking and aging, the factors that influence lung function decline to incident chronic obstructive pulmonary disease (COPD) remain unclear. Advancements have been made in categorizing COPD into emphysema and airway predominant disease subtypes; however, predicting which healthy individuals will progress to COPD is difficult because they can exhibit profoundly different disease trajectories despite similar initial risk factors. This study aimed to identify clinical, genetic, and radiological features that are directly linked-and subsequently predict-abnormal lung function. We employed graph modeling on 2,643 COPDGene participants (aged 45 to 80 years, 51.25% female, 35.1% African Americans; enrollment 11/2007-4/2011) with smoking history but normal spirometry at study enrollment to identify variables that are directly linked to future lung function abnormalities. We developed logistic regression and random forest predictive models for distinguishing individuals who maintain lung function from those who decline. Of the 131 variables analyzed, 6 were identified as informative to future lung function abnormalities, namely forced expiratory flow in the middle range (FEF25-75%), average lung wall thickness in a 10 mm radius (Pi10), severe emphysema, age, sex, and height. We investigated whether these features predict individuals leaving GOLD 0 status (normal spirometry according to Global Initiative for Obstructive Lung Disease (GOLD) criteria). Linear models, trained with these features, were quite predictive (area under receiver operator characteristic curve or AUROC = 0.75). Random forest predictors performed similarly to logistic regression (AUROC = 0.7), indicating that no significant nonlinear effects were present. The results were externally validated on 150 participants from Specialized Center for Clinically Oriented Research (SCCOR) cohort (aged 45 to 80 years, 52.7% female, 4.7% African Americans; enrollment: 7/2007-12/2012) (AUROC = 0.89). The main limitation of longitudinal studies with 5- and 10-year follow-up is the introduction of mortality bias that disproportionately affects the more severe cases. However, our study focused on spirometrically normal individuals, who have a lower mortality rate. Another limitation is the use of strict criteria to define spirometrically normal individuals, which was unavoidable when studying factors associated with changes in normalized forced expiratory volume in 1 s (FEV1%predicted) or the ratio of FEV1/FVC (forced vital capacity). This study took an agnostic approach to identify which baseline measurements differentiate and predict the early stages of lung function decline in individuals with previous smoking history. Our analysis suggests that emphysema affects obstruction onset, while airway predominant pathology may play a more important role in future FEV1 (%predicted) decline without obstruction, and FEF25-75% may affect both.

Prevalence, patterns, and factors associated with abnormal lung function among children with sickle cell disease in Uganda: a cross-sectional study

BackgroundPulmonary complications are common among children with sickle cell disease (SCD). However, there is little literature on associated lung function abnormalities in Uganda. We aimed to determine the prevalence, patterns, and factors associated with abnormal lung function among children with SCD in a tertiary care hospital in Uganda.MethodA cross-sectional study was conducted among children aged 6 to 18 years at the SCD clinic (SCC) of Mulago National Super-Specialized Hospital between January 2020 and April 2021. Data on sociodemographic and clinical characteristics was collected using a standardized questionnaire. Laboratory investigations, including a complete blood count and serum lactate dehydrogenase (LDH), were done. Spirometry was performed following the ATS/ERS standards. Multivariable modified Poisson regression analysis was performed to determine factors associated with abnormal lung function.ResultsA total of 332 participants were enrolled. The mean age was 11.7 ± 3.4 years, and 184 (55.4%) were female. Overall, 126 (37.9%) participants had abnormal lung function: 67/126 (53.2%) restrictive, 57/126 (45.2%) obstructive, and 2/126 (1.6%) mixed-ventilatory patterns. Factors associated with abnormal lung function were; serum LDH level > 600UL (aIRR: 1.89 95% CI: 1.2 — 7.4, p = 0.049), a history of acute chest syndrome (aIRR: 1.55, 95% CI: 1.06–2.25, p = 0.024), wasting (aIRR: 1.33, 95%CI: 1.02 — 1.72, p = 0.032), and use of charcoal for household cooking (aIRR: 1.49, 95% CI: 1.03–2.15, p = 0.035).ConclusionMore than one-third of children with SCD in Uganda have lung function abnormalities. Strategies to improve nutrition, reduce exposure to charcoal smoke, and monitoring serum LDH levels may be important in preventing or managing abnormal lung function in this population. The identification of reversible and irreversible airway obstruction in children with sickle cell disease also highlights the need for targeted interventions to address these specific patterns of abnormal lung function.