Lower Lung Function Research Articles

Early-life and health behaviour influences on lung function in early adulthood.

Early-life exposures may influence lung function at different stages of the life course. However, the relative importance of characteristics at different stages of infancy and childhood are unclear. To examine the associations and relative importance of early-life events on lung function at age 24 years. We followed 7545 children from the Avon Longitudinal Study of Parents and Children from birth to 24 years. Using previous knowledge, we classified an extensive list of putative risk factors for low lung function, covering sociodemographic, environmental, lifestyle and physiological characteristics, according to timing of exposure: 1) demographic, maternal and child; 2) perinatal; 3) postnatal; 4) early childhood; and 5) adolescence characteristics. Lung function measurements (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC and forced expiratory flow at 25-75% of FVC) were standardised for sex, age and height. The proportion of the remaining variance explained by each characteristic was calculated. The association and relative importance (RI) of each characteristic for each lung function measure was estimated using linear regression, adjusted for other characteristics in the same and previous categories. Lower maternal perinatal body mass index (BMI), lower birthweight, lower lean mass and higher fat mass in childhood had the largest RI (0.5-7.7%) for decreased FVC. Having no siblings, lower birthweight, lower lean mass and higher fat mass were associated with decreased FEV1 (RI 0.5-4.6%). Higher lean mass and childhood asthma were associated with decreased FEV1/FVC (RI 0.6-0.8%). Maternal perinatal BMI, birthweight, childhood lean and fat mass and early-onset asthma are the factors in infancy and childhood that have the greatest influence on early-adult lung function.

Effect of diagnosis delay on pulmonary function in children with asthma

BackgroundThe effects of a delayed diagnosis of asthma on lung function in children have not been well investigated. Therefore, a retrospective cohort study was conducted in a children’s hospital to analyse the effect of delayed diagnosis time on lung function in children with asthma.MethodsWe conducted a retrospective cohort study in Jinan Children's Hospital from January 1, 2010, to December 31, 2020. All children were divided into different groups according to the presence or absence of rhinitis, age at first onset (first coughing and wheezing attack) and delayed diagnosis duration (≤ 3 months, 3–12 months, 1–3 years, 3–5 years and > 5 years).ResultsA total of 1,014 children with asthma were included in this study. The median (quartile) delay in asthma diagnosis among all participants was 11 (2, 26) months. The shortest delay in diagnosis time was on the same day of onset, and the longest delay in diagnosis time was 10 years. The median (quartile) duration of delayed diagnosis was 10 (2, 26) months in 307 asthmatic children without rhinitis and 11 (2, 26) months in 707 children with asthma and rhinitis (P < 0.05). The delayed diagnosis time was shorter among female children than among male children (P < 0.05), and the first %predicted forced volume capacity (FVC%pred) results for females were higher than those for males (P = 0.036). The children whose age at first asthma onset was ≤ 3 years had a longer delayed diagnosis duration than those whose age at first onset was > 3 years (P < 0.05). The FVC%pred and %predicted forced expiratory volume in 1 s (FEV1%pred) in the first and second pulmonary function tests were significantly lower in the five delayed diagnosis groups (all P < 0.05). After standardised treatment for 3–6 months, FVC%pred showed a significant difference in the third test among the 5 groups (P < 0.05), but the other pulmonary function indices showed no significant difference. Logistic regression analysis showed that longer delay and young age of onset were associated with lower lung function (P < 0.05), whereas sex, rhinitis and eczema had no significant effects (all P > 0.05) on FVC%pred and FEV1%pred.ConclusionAlthough delayed asthma diagnosis can lead to lung function impairment in children with asthma, lung function can be improved quickly after standardised treatment. Therefore, early asthma diagnosis and standardised treatment are very important.

Lifetime lung function trajectories and COPD: when the train derails

Increasing recognition that chronic respiratory disease originates in early life has shifted the paradigm away from traditional concepts of chronic obstructive pulmonary disease (COPD) as solely a smoker's disease. 1 Martinez FD Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016; 375: 871-878 Crossref PubMed Scopus (277) Google Scholar Building on Fletcher and Peto's landmark publication highlighting smoking-related decline of FEV1, 2 Fletcher C Peto R The natural history of chronic airflow obstruction. BMJ. 1977; 1: 1645-1648 Crossref PubMed Scopus (1800) Google Scholar multiple cohort studies have since implicated altered lung function trajectories originating in childhood in the accelerated development of lung disease. 3 Berry CE Billheimer D Jenkins IC et al. A distinct low lung function trajectory from childhood to the fourth decade of life. Am J Respir Crit Care Med. 2016; 194: 607-612 Crossref PubMed Scopus (114) Google Scholar , 4 Lange P Celli B Agustí A et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N Engl J Med. 2015; 373: 111-122 Crossref PubMed Scopus (346) Google Scholar , 5 McGeachie MJ Yates KP Zhou X et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016; 374: 1842-1852 Crossref PubMed Scopus (350) Google Scholar , 6 Stern DA Morgan WJ Wright AL Guerra S Martinez FD Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007; 370: 758-764 Summary Full Text Full Text PDF PubMed Scopus (429) Google Scholar This work has revealed that many individuals tend to track along a lung function percentile established in childhood, such that those who begin life at a lower lung function percentile because of adverse perinatal or chronic childhood respiratory conditions are hindered from reaching maximal peak lung function as young adults. Even with the normal age-related rate of lung function decline, these individuals stay on a path with an increased lifetime risk for COPD. Importantly, multiple identified early-life risk factors—including those experienced in utero—alter developmental programming, affecting the timing and course of progression to chronic lung disease. 7 Postma DS Bush A van den Berge M Risk factors and early origins of chronic obstructive pulmonary disease. Lancet. 2015; 385: 899-909 Summary Full Text Full Text PDF PubMed Scopus (318) Google Scholar Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort studyTo our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. Full-Text PDF

Risk Factors for Lung Function Decline in Pediatric Asthma under Treatment: A Retrospective, Multicenter, Observational Study.

Background: Childhood asthma is a major risk for low lung function in later adulthood, but what factors in asthma are associated with the poor lung function during childhood is not known. Objective: To identify clinical factors in children with asthma associated with low or declining lung function during the treatment. Methods: We enrolled children with asthma who had been treated throughout three age periods, i.e., 6–9, 10–12, and 13–15 years old, at seven specialized hospitals in Japan. Clinical information and lung function measurements were retrieved from the electronic chart systems. To characterize the lung function trajectories during each age period, we evaluated the forced expiratory volume 1 (FEV1) with % predicted values and individual changes by the slope (S) from linear regression. We defined four trajectory patterns: normal (Group N) and low (Group L), showing %FEV1 ≥80% or <80% throughout all three periods; upward (Group U) and downward (Group D), showing S ≥ 0 or S < 0%. Logistic regression analysis was performed to compare factors associated with the unfavorable (D/L) versus favorable (N/U) groups. Results: Among 273 eligible patients, 197 (72%) were classified into Group N (n = 150)/U (n = 47), while 76 (28%) were in Group D (n = 66)/L (n = 10). A history of poor asthma control, long-acting beta2 agonist use, and a lower height Z-score during 13–15 years were associated with an unfavorable outcome (Group D/L). Conversely, inhaled corticosteroid (ICS) use during 10–12 years and high-dose ICS use during 13–15 years were associated with a favorable outcome (Group N/U). Conclusion: We identified several factors that are associated with unfavorable lung function changes in pediatric asthma. Attention should be paid to the possible relationship between yearly changes in lung function and poor asthma control, use of ICS (and its dose) and use of LABA.

Lung function in young adults born small for gestational age at term.

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NICEFIT-A Prospective, Non-Interventional, and Multicentric Study for the Management of Idiopathic Pulmonary Fibrosis with Antifibrotic Therapy in Taiwan.

Idiopathic pulmonary fibrosis (IPF) causes progressive lung fibrosis with subsequent fatality and has limited treatment options. NICEFIT is the first Taiwan-based prospective, observational, and non-interventional registry for IPF progression under routine clinical practice in Taiwan. Data on 101 patients (aged 74.6 ± 9.1 years and 83.2% men) with IPF were collected over 2 years (2018−2020) from medical centers in Taiwan at baseline, 1 month, and subsequent 3-month intervals. Treated patients (n = 88) received the antifibrotics nintedanib or pirfenidone, compared with the untreated group (n = 13). The 2-year assessment revealed overall preserved lung functionality in the treated patients, with insignificant changes from baseline for percent predicted forced vital capacity or FVC (±1.7%). The presence of respiratory comorbidities significantly increased the risk of both AE and death (with or without AE) over the full study duration. Furthermore, the decline of predicted FVC significantly increased with the risk of acute exacerbations (AE) in the second year. Overall, antifibrotic medication was beneficial in stalling IPF progression, reducing AEs, and delaying mortality in the treated cohort, despite their lower baseline lung functions. Further, no new safety concerns over antifibrotic treatments were observed for the Taiwanese population.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3

Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.

Image Phenotyping of Preterm-Born Children Using Hyperpolarized 129Xe Lung Magnetic Resonance Imaging and Multiple-Breath Washout.

Rationale: Preterm birth is associated with low lung function in childhood, but little is known about the lung microstructure in childhood. Objectives: We assessed the differential associations between the historical diagnosis of bronchopulmonary dysplasia (BPD) and current lung function phenotypes on lung ventilation and microstructure in preterm-born children using hyperpolarized 129Xe ventilation and diffusion-weighted magnetic resonance imaging (MRI) and multiple-breath washout (MBW). Methods: Data were available from 63 children (aged 9-13 yr), including 44 born preterm (⩽34 weeks' gestation) and 19 term-born control subjects (⩾37 weeks' gestation). Preterm-born children were classified, using spirometry, as prematurity-associated obstructive lung disease (POLD; FEV1 < lower limit of normal [LLN] and FEV1/FVC < LLN), prematurity-associated preserved ratio of impaired spirometry (FEV1 < LLN and FEV1/FVC ⩾ LLN), preterm-(FEV1 ⩾ LLN) and term-born control subjects, and those with and without BPD. Ventilation heterogeneity metrics were derived from 129Xe ventilation MRI and SF6 MBW. Alveolar microstructural dimensions were derived from 129Xe diffusion-weighted MRI. Measurements and Main Results: 129Xe ventilation defect percentage and ventilation heterogeneity index were significantly increased in preterm-born children with POLD. In contrast, mean 129Xe apparent diffusion coefficient, 129Xe apparent diffusion coefficient interquartile range, and 129Xe mean alveolar dimension interquartile range were significantly increased in preterm-born children with BPD, suggesting changes of alveolar dimensions. MBW metrics were all significantly increased in the POLD group compared with preterm- and term-born control subjects. Linear regression confirmed the differential effects of obstructive disease on ventilation defects and BPD on lung microstructure. Conclusion: We show that ventilation abnormalities are associated with POLD, and BPD in infancy is associated with abnormal lung microstructure.

Vitamin D status and asthma, lung function, and hospitalization among British adults.

BackgroundVitamin D has been known to be associated with asthma. However, the association between vitamin D status and asthma, lung function as well as hospitalization among adults remains unclear.ObjectiveTo investigate the role of serum vitamin D in asthma prevalence, lung function, and asthma control in adults.MethodsMultivariable logistic regression was applied to assess the relationship between serum vitamin D and asthma prevalence, lung function (FEV1, FVC, and FEV1/FVC), current wheeze, and asthma-linked hospitalizations in a cross-sectional study of 435,040 adults aged 37–73 years old from the UK Biobank.ResultsCompared to vitamin D deficiency, the odds of asthma were decreased by 6.4% [adjusted odds ratio (aOR) = 0.936; 95% CI: 0.911–0.962; p < 0.001] and 9.8% (aOR = 0. 0.902; 95% CI: 0.877–0. 0.927; p < 0.001) in individuals with insufficient and optimal vitamin D concentration, respectively, in the fully adjusted model. In total asthmatic patients, serum vitamin D was obviously and positively related with FEV1 (β = 1.328 ml, 95% CI = 0.575–2.080), FVC (β = 2.018 ml, 95% CI = 1.127–2.908), and FEV1/FVC (β = 0.006%, 95% CI = 0.002–0.010). Asthmatic patients whose vitamin D level was in the deficient category had 9.3–19.9% higher odds of current wheeze than insufficient categories (aOR = 0.907; 95% CI: 0.861–0.957; p < 0.001) and optimal categories (aOR = 0.801; 95% CI: 0.759–0.845; p < 0.001), but the relationship between vitamin D and asthma hospitalization was not significant.ConclusionVitamin D deficiency was related to higher odds of asthma and current wheeze, and lower lung function in a large sample size study of British adults. Our results indicate a potential positive impact of serum vitamin D on asthma occurrence and disease control in adults.

Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study.

Physical activity, which can be affected by airflow limitation and extrapulmonary comorbidities, has been reported to be reduced in patients with chronic obstructive pulmonary disease, and reduced physical activity is associated with higher risks of exacerbation and mortality. The aim of the present study is to elucidate the comprehensive effect of extrapulmonary comorbidities on physical activity in Japanese patients with chronic obstructive pulmonary disease, of which evidence is lacking. We conducted a cross-sectional study with a series of tests, including lung function, physical activity, symptom scores, and parameters for comorbidities. Sixty outpatients with stable disease were enrolled, and the relationship between the parameters and physical activity was evaluated. Physical activity was assessed over 7 consecutive days using a triaxial accelerometer, which records total daily energy expenditure, step count, and walking time. Cardiovascular status was assessed via echocardiography, and pulmonary artery pressure was estimated using Doppler sonography. As to mental status, depression and anxiety were assessed using the Self-Rating Depression Scale and State-Trait Anxiety Inventory, respectively. Physical activity level was significantly correlated with step count, walking time, body mass index, lean body mass index, lung function, pulmonary artery pressure, depression, anxiety, and serum total cholesterol level. In a median regression model analysis, low lung function, low lean body mass index, depression, and low serum total cholesterol level were independently associated with decreased physical activity level. These findings suggest that physical inactivity is affected by multiple extrapulmonary factors, including skeletal muscle dysfunction, depressive symptoms, and nutritional state, in Japanese patients with chronic obstructive pulmonary disease.

The Dietary Inflammatory Index and Early COPD: Results from the National Health and Nutrition Examination Survey.

We examined 3962 people aged 20 to 49 years who had information on spirometry testing and underwent a 24 h dietary recall interview from the 2007–2012 National Health and Nutrition Examination Survey (NHANES) and used multivariable logistic regression to evaluate associations between Dietary Inflammatory Index (DII, a pro-inflammatory diet) and early COPD and lung function. The overall prevalence of early COPD was 5.05%. Higher DII was associated with increased odds of early COPD (quartile 4 vs. 1, the OR = 1.657, 95% CI = 1.100–2.496, p = 0.0156). In a full-adjusted model, each unit of increase in DII score was associated with a 90.3% increase in the risk of early COPD. Higher DII is significantly associated with lower FEV1 and FVC among individuals with early COPD, each unit increment in the DII was significantly associated with 0.43 L–0.58 L decrements in FEV1 (β = –0.43, 95% CI = −0.74, −0.12) and FVC (β = −0.58, 95% CI = −1.01, −0.16). These findings demonstrate that higher consumption of a pro-inflammatory diet may contribute to an increased risk of early COPD and lower lung function, and further support dietary interventions as part of a healthy lifestyle in order to preserve lung function and prevent or improve COPD.

Prevalence of Asthma among Norwegian Elite Athletes.

Asthma is a common problem among elite athletes and represents a health risk interfering with the athlete's performance status. This study aimed to evaluate the asthma prevalence among Norwegian summer and winter elite athletes and asthma prevalence across sport categories. We also aimed to examine whether bronchial hyperresponsiveness (BHR), lung function, fraction of exhaled nitric oxide (FENO), and allergy status differed between asthmatic and non-asthmatic elite athletes. Norwegian athletes qualifying for the Beijing Olympic Summer Games 2008 (n = 80) and the Vancouver Olympic Winter Games 2010 (n = 55) were included. The athletes underwent clinical respiratory examination including lung function measurement, methacholine bronchial challenge for assessment of BHR, FENO, and skin prick testing. Asthma was diagnosed based on respiratory symptoms and clinical examination including objective measurements. Asthma was more prevalent among winter athletes (50%) than summer athletes (20%). Thirty-three (52%) endurance athletes, 3 (6%) team sport athletes, and 7 (33%) technical sport athletes had medically diagnosed asthma. Significantly lower lung function (p < 0.001) and higher prevalence of severe BHR (p < 0.001) were found in asthmatic athletes compared with non-asthmatic athletes. Asthma is common among Norwegian elite athletes, with winter and endurance athletes showing the highest prevalence. Asthmatic athletes were characterized by lower lung function and more severe BHR compared with non-asthmatic counterparts. The high prevalence among winter and endurance athletes demonstrates a need for increased attention to prevent and reduce the prevalence of asthma among those athletes.

Causal Inference Analysis for Poorly Soluble Low Toxicity Particles, Lung Function, and Malignancy.

Poorly soluble low toxicity particles such as carbon black and titanium dioxide have raised concern about possible nonmalignant and malignant pulmonary effects. This paper illustrates application of causal inference analysis to assessing these effects. A framework for analysis is created using directed acyclic graphs to define pathways from exposure to potential lung cancer or chronic airflow obstruction outcomes. Directed acyclic graphs define influences of confounders, backdoor pathways, and analytic models. Potential mechanistic pathways such as intermediate pulmonary inflammation are illustrated. An overview of available data for each of the inter-node links is presented. Individual empirical epidemiologic studies have limited ability to confirm mechanisms of potential causal relationships due to the complexity of causal pathways and the extended time course over which disease may develop. Therefore, an explicit conceptual and graphical framework to facilitate synthesizing data from several studies to consider pulmonary inflammation as a common pathway for both chronic airflow obstruction and lung cancer is suggested. These methods are useful to clarify potential bona fide and artifactual observed relationships. They also delineate variables which should be included in analytic models for single study data and biologically relevant variables unlikely to be available from a single study.

Hierarchical cluster analysis based on disease-associated manifestations of patients with lymphangioleiomyomatosis: An analysis of the national database of designated intractable diseases of Japan

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease with variable manifestations and differing rates of progression among individuals. Classification of its phenotypes is an issue for consideration. We hypothesized that clinical manifestations associated with LAM cluster together and identifying these associations would be useful for identifying phenotypes. Using cross-sectional data from the National Database of Designated Intractable Diseases of Japan, we performed a hierarchical cluster analysis based on disease-associated manifestations. Four clusters were identified from 404 patients (50.4% of 801 LAM patients registered in 2016). Patients in cluster 1 had only dyspnea on exertion, relatively low lung function, the earliest onset age, and the lowest prevalence of tuberous sclerosis complex (TSC). Those in cluster 2 had various manifestations with the highest prevalence of TSC. Patients in cluster 3 had major respiratory symptoms (cough, sputum, or dyspnea on exertion) or fatigue and the lowest lung function. Those in cluster 4 were asymptomatic and had the latest onset age, shortest disease duration, and relatively high prevalence of TSC. Patients in cluster 1 had the highest rate of receiving mechanistic target of rapamycin (mTOR) inhibitor treatment, suggesting that cluster 1 included those with declining lung function for which mTOR inhibitor treatment was required. Hierarchical cluster analysis based on manifestations data identified four clusters. The characteristics of cluster 1 are noteworthy in relation to the indication for mTOR inhibitor treatment. A cluster analysis of accumulated and longitudinal data that allows valid clustering and outcome comparisons is required in the future.

Tollip Inhibits IL-33 Release and Inflammation in Influenza A Virus-Infected Mouse Airways

Respiratory influenza A virus (IAV) infection continues to pose significant challenges in healthcare of human diseases including asthma. IAV infection in mice was shown to increase IL-33, a key cytokine in driving airway inflammation in asthma, but how IL-33 is regulated during viral infection remains unclear. We previously found that a genetic mutation in Toll-interacting protein (Tollip) was linked to less airway epithelial Tollip expression, increased neutrophil chemokines, and lower lung function in asthma patients. As Tollip is involved in maintaining mitochondrial function, and mitochondrial stress may contribute to extracellular ATP release and IL-33 secretion, we hypothesized that Tollip downregulates IL-33 secretion via inhibiting ATP release during IAV infection. Wild-type and Tollip knockout (KO) mice were infected with IAV and treated with either an ATP converter apyrase or an IL-33 decoy receptor soluble ST2 (sST2). KO mice significantly lost more body weight and had increased extracellular ATP, IL-33 release, and neutrophilic inflammation. Apyrase treatment reduced extracellular ATP levels, IL-33 release, and neutrophilic inflammation in Tollip KO mice. Excessive lung neutrophilic inflammation in IAV-infected Tollip KO mice was reduced by sST2, which was coupled with less IL-33 release. Our data suggest that Tollip inhibits IAV infection, potentially by inhibiting extracellular ATP release and reducing IL-33 activation and lung inflammation. In addition, sST2 may serve as a potential therapeutic approach to mitigate respiratory viral infection in human subjects with Tollip deficiency.

A longitudinal analysis of early lung function trajectory in survivors of childhood Hodgkin lymphoma.

Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%. This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy. In this single-center, 20-year retrospective cohort study, we included patients who were <18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1-2 years after treatment completion, some children with these risk factors did not. Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

Long-term clinical course and outcomes in patients with lymphangioleiomyomatosis

BackgroundLymphangioleiomyomatosis (LAM) is a rare multisystemic disorder with various clinical manifestations. Despite the recognition of several prognostic factors, the long-term clinical course and prognosis of patients with LAM in the era of sirolimus therapy are not established.MethodsThe clinical data of 104 patients with LAM were retrospectively analyzed. Death or lung transplantation was defined as the primary outcome. Disease progression (DP) was defined as a 10% absolute decline in forced expiratory volume in one second (FEV1).ResultsThe mean age of all patients was 40.3 years. Over a median follow-up period of 7.1 years, of all patients, 6.7% died and 1.9% underwent lung transplantation, while of 92 patients with serial lung function data, 35.9% experienced DP. The 5-year and 10-year overall survival rates were 93.0% and 90.9%, respectively. The multivariable Cox analysis revealed that older age (hazard ratio [HR]: 1.136, P = 0.025), lower FEV1 (HR: 0.956, P = 0.026) or diffusing capacity for carbon monoxide (HR: 0.914, P = 0.003), and shorter distance during the 6-min walk test (HR: 0.993, P = 0.020) were independent prognostic factors for mortality. A propensity score-matched comparative analysis performed between patients who received sirolimus therapy and those who did not, found no differences in survival, DP, complications, and lung function decline rate.ConclusionsOver a follow-up period of approximately 7 years, one-tenth of all patients experienced death, while one-third experienced DP. Older age, lower lung function, and reduced exercise capacity were associated with a poor prognosis in patients with LAM.

Association of inflammation and lung function decline caused by personal PM2.5 exposure: a machine learning approach in time-series data.

Numerous studies focused on the association between lung function impairment and inflammation caused by fine particulate matter (PM2.5), but the causal relationships are difficult to clarify. In the current study, twenty healthy Chinese young adults who participated in 7days of observation every four seasons were enrolled, and autoregression models (AM) and classification and regression trees (CART) in a machine learning framework were applied to analyze the association among PM2.5 exposure, inflammation, and lung function from a data structure perspective. There were strong cross-correlations between personal dose of PM2.5 (Dw) and lung functions (vital capacity (VC), forced vital capacity (FVC), etc.). These cross-correlation coefficients were associated with inflammatory indicators (uteroglobin (UG), serum amyloid (SAA), and fractional exhaled nitric oxide (FeNO)). CART reported that inflammatory indicators UG and SAA had the predictive ability of the directional association between Dw and FVC at 1-day lag and that high levels of UG and SAA predicted that PM2.5 exposure induced lung function decline. Consistently, lower lung function indicators at a 2-day lag after personal PM2.5 exposure predicted the high value of inflammatory indicator FeNO. Taken together, we applied machine learning algorithms to analyze repeated measurement data, finding that inflammation and lung function decline caused by PM2.5 could affect each other.

The Impact of Insulin Resistance on Loss of Lung Function and Response to Treatment in Asthma.

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (<3.0), moderate (3.0-5.0), or severe (>5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to β-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P < 0.001 for both comparisons). Conclusions: IR is common in asthma and is associated with lower lung function, accelerated loss of lung function, and suboptimal lung function responses to bronchodilator and corticosteroid treatments. Clinical trials in patients with asthma and IR are needed to determine if improving IR might also improve lung function.

Associations of physical condition with lung function and asthma in adolescents from the general population.

BackgroundThe relation of physical condition with respiratory outcomes in adolescents is unclear. We examined the hypothesis that adolescents with a lower physical condition represented by a lower cardiorespiratory fitness and physical activity, and a higher screen time have a lower lung function and higher risk of asthma.MethodsIn a population‐based prospective cohort study on 4854 children aged 13 years, we assessed cardiorespiratory fitness by using the peak work rate measured by the steep ramp test. Information on physical activity and screen time was obtained by self‐reported questionnaires. Lung function was measured by spirometry and current asthma was assessed by a parental‐reported questionnaire.ResultsTaking sociodemographic, lifestyle, and growth‐related confounders and multiple hypothesis testing into account, a 1 SD lower cardiorespiratory fitness was associated with a lower FEV1, FVC, and FEF75 (Z‐score difference (95% CI): −0.31 (−0.35, −0.28), −0.30 (−0.33, −0.26), −0.13 (−0.17, −0.10), respectively), and a higher risk of asthma (Odds Ratio (95% CI) 1.25 (1.06, 1.46)). A 1 SD higher screen time was associated with a lower FVC (Z‐score difference (95% CI): −0.06 (−0.10, −0.03)). Physical activity and screen time were not related to asthma. Results did not materially change after additional adjustment for respiratory outcomes at an earlier age.ConclusionAdolescents with a lower cardiorespiratory fitness had a lower lung function and a higher risk of asthma. Those with a higher screen time had a lower FVC. Further studies are needed to explore the effect of improvements in physical condition on long‐term respiratory outcomes.