Lung Function Measurements Research Articles

A lifecourse approach to the relationship between lung function and cognition function in late life: findings from the Mysore studies of Natal effect on Ageing and Health (MYNAH) in South India

Background: Emerging evidence from high income settings indicates that lung function may be an independent determinant of cognitive abilities in late life. Despite a high burden of chronic lung disorders and neurocognitive disorders, there are limited data exploring the relationship between lung and cognitive function in later life in low- and middle-income (LMIC) settings. Methods: Between 2013 and 2016, 721 men and women from the Mysore Birth Records Cohort in South India, aged 55-80 years, were retraced and underwent standardised assessments for sociodemographic characteristics, cardiometabolic risk factors, lung function, cognitive function and mental health. Approximately 20 years earlier, a subset of them had assessments for cardiometabolic risk factors (n=522) and lung function (n=143). Results: Forced Expiratory Volume at one second (FEV1) and six seconds (FEV6) were higher among men than women. Women had higher immediate and delayed recall scores compared to men. Multivariate models indicated that those with lower FEV1 (lts) and FEV1/FEV6 ratio in late life had lower composite cognitive score (SD, standard deviation), independent of growth and environment in early life and childhood, attained education, socioeconomic position, cardiometabolic disorders in mid-and late life and lifestyle factors (0.29 SD per litre 95% confidence interval [CI] (0.10, 0.50) p=0.006 for FEV1 and 1.32 SD (0.20, 2.50) p=0.02 for FEV1/FEV6 ratio). Lung function in midlife was unrelated to cognitive outcomes in late life. Conclusions: Causality cannot be inferred from cross sectional associations. Therefore, causality is best explored in longitudinal studies with serial, but contemporaneous measurements of both lung and cognitive function. Mechanistic studies that examine the role of shared risk factors like environmental pollutants and biomass exposure on this relationship are urgently required in LMICs.

Endolysosomal Cation Channels and Lung Disease.

Endolysosomal cation channels are emerging as key players of endolysosomal function such as endolysosomal trafficking, fusion/fission, lysosomal pH regulation, autophagy, lysosomal exocytosis, and endocytosis. Diseases comprise lysosomal storage disorders (LSDs) and neurodegenerative diseases, metabolic diseases, pigmentation defects, cancer, immune disorders, autophagy related diseases, infectious diseases and many more. Involvement in lung diseases has not been a focus of attention so far but recent developments in the field suggest critical functions in lung physiology and pathophysiology. Thus, loss of TRPML3 was discovered to exacerbate emphysema formation and cigarette smoke induced COPD due to dysregulated matrix metalloproteinase 12 (MMP-12) levels in the extracellular matrix of the lung, a known risk factor for emphysema/COPD. While direct lung function measurements with the exception of TRPML3 are missing for other endolysosomal cation channels or channels expressed in lysosome related organelles (LRO) in the lung, links between those channels and important roles in lung physiology have been established such as the role of P2X4 in surfactant release from alveolar epithelial Type II cells. Other channels with demonstrated functions and disease relevance in the lung such as TRPM2, TRPV2, or TRPA1 may mediate their effects due to plasma membrane expression but evidence accumulates that these channels might also be expressed in endolysosomes, suggesting additional and/or dual roles of these channels in cell and intracellular membranes. We will discuss here the current knowledge on cation channels residing in endolysosomes or LROs with respect to their emerging roles in lung disease.

Serum and sputum MMP-9/TIMP-1 in winter sports athletes and swimmers: relationships with airway function

Introduction Skiers and swimmers present characteristics of airway inflammation and remodelling of the extracellular matrix similar to what is observed in mild asthma. We aimed to compare serum and sputum MMP-9/TIMP-1 levels, to assess the balance between airway fibrogenesis and inflammation process in both categories of athletes, and to observe its seasonal variations in winter sports athletes. Methods We conducted a retrospective study. Winter sports athletes (n = 41), swimmers (n = 25) and healthy nonathletes (n = 10) had blood sampling, lung function measurement, skin prick tests, eucapnic voluntary hyperpnoea challenge, methacholine inhalation test, and induced sputum analysis. Twelve winter sport athletes performed the tests during both summer and winter. Serum and sputum biomarkers were measured by ELISA. Results No significant difference in serum or sputum MMP-9/TIMP-1 ratio was observed between groups, nor relationship with airway function or responsiveness. Serum MMP-9/TIMP-1 ratio was higher during the summer in winter sport athletes compared with winter season (median [Interquartile range]: 3.65 [2.47-4.03] ng.ml−1 and 1.27 [0.97-1.62] ng.ml−1, respectively, p = 0.005). Sputum MMP-9 correlated with methacholine PC20 (r = 0.45, p = 0.019) and serum cc16/SP-D ratio (r = −0.47, p = 0.013). Conclusion MMP-9/TIMP-1 ratio in sputum or serum may fluctuate with training or environment but does not correlate with airway function or responsiveness in athletes.

Persistent overweight or obesity, lung function, and asthma exacerbations in Puerto Rican youth

BackgroundWhether persistent overweight or obesity affects lung function or asthma morbidity in youth is unclear. ObjectiveTo evaluate overweight or obesity that persists between school age and adolescence and change in lung function and total immunoglobulin (Ig)E and severe asthma exacerbations in Puerto Rican youth. MethodsProspective study of 340 Puerto Rican youth assessed at 2 visits, the first at ages 6 to 14 years and the second at ages 9 to 20 years. Persistent overweight or obesity was defined as a body mass index z-score greater than or equal to 85th percentile at both visits. Outcomes of interest were change in percent predicted (%pred) lung function measures and total IgE between study visits and severe asthma exacerbations in the year before visit 2. Logistic or linear regression was used for multivariable analysis. ResultsIn multivariable analysis, persistently overweight or obese subjects had changes in %pred forced expiratory volume in 1 second (FEV1) (β = −5.07%; 95% confidence interval, −1.51% to −8.62%; P < .01) and %pred FEV1 to forced vital capacity (FVC) ratio (β = −2.85%; 95% confidence interval, −0.18% to −5.51%; P = .04) which were lower than those observed in subjects with normal weight at both study visits (control subjects). Compared with control subjects, those who were persistently overweight or obese and those who became overweight or obese at visit 2 had increased odds of more than or equal to 1 severe asthma exacerbation in the year before visit 2. There was no significant association between persistent overweight or obesity and change in %pred FVC or total IgE (P > .20 for both instances). ConclusionIn a prospective study of Puerto Rican youth, persistently overweight or obese subjects had lower changes in FEV1 or FEV1 to FVC ratio and higher odds of severe asthma exacerbations than subjects of normal weight.

Depth of cervical plexus block and phrenic nerve blockade: a randomized trial

Background and objectivesCervical plexus blocks are commonly used to facilitate carotid endarterectomy (CEA) in the awake patient. These blocks can be divided into superficial, intermediate, and deep blocks by their...

Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda

BackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure.MethodsWe measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status.ResultsOf 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (β = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT.ConclusionsImpaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

The association between periodontitis and lung function: Results from the National Health and Nutrition Examination Survey 2009 to 2012.

We aimed to explore the association between periodontitis and lung function in the United States. The data was based on the National Health and Nutrition Examination Survey (NHANES) 2009 to 2012. Periodontitis was defined following the CDC/AAP (Centers for Disease Control and Prevention/American Academy of periodontology) classification. Lung function measurements included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear regression and binary logistic regression were used to explore the association between periodontitis and lung function measurements. Restricted cubic spline was used to assess the dose-response relationships between the mean attachment loss (AL), the mean probing depth (PD) and spirometry-defined airflow obstruction (FEV1/FVC<0.7). A total of 6313 adults aged 30 years or older were included. Compared to those with non-periodontitis, the multivariate-adjusted odds ratios (ORs) of airflow obstruction for moderate and severe periodontitis were 1.38 (95% CI: 1.01 to 1.75) and 1.47 (95% CI: 1.06 to 2.01), the β coefficients of FEV1 for moderate and severe periodontitis were -130.16 (95% CI: -172.30 to -88.01) and -160.46 (95% CI: -249.94 to -70.97), the β coefficients of FVC for moderate and severe periodontitis were -100.96 (95% CI: -155.08 to -46.85) and -89.89 (95% CI: -178.45 to -1.33), the β coefficients of FEV1/FVC for moderate and severe periodontitis were -0.01 (95% CI: -0.02 to -0.01) and -0.02 (95% CI: -0.03 to -0.01). In stratified analyses, the multivariate-adjusted ORs of airflow obstruction for the moderate and severe periodontitis were 1.27 (95% CI: 0.84 to 1.93) and 2.31 (95% CI: 1.10 to 4.83) in former smokers, 1.84 (95% CI: 1.03 to 3.30) and 1.79 (95% CI: 1.02 to 3.16) in current smokers, with no significant association observed in never smokers. Mean clinical AL and mean PD were negatively associated with FEV1, FVC, and FEV1/FVC in never, former, and current smokers. Dose-response relationship analysis showed that the risk of airflow obstruction increased with increasing mean clinical AL and mean PD, and showed a non-linear dose-response relationship. Our study suggested that moderate and severe periodontitis might be associated with the decline of lung function in the United States of America.

The Effect of Deployment on Pulmonary Function in Military Personnel With Asthma.

Military personnel with a diagnosis of asthma report increased respiratory symptoms in the deployment and post-deployment periods. The long-term effect of deployment on pulmonary function in this population is unknown. This study sought to determine the effect of deployment on post-deployment pulmonary function in active duty military personnel with asthma. A retrospective chart review of active duty military personnel with deployment to southwest Asia and an ICD-9 diagnosis of asthma with documented pre- and post-deployment spirometry was performed. A total of 642 active duty individuals with a diagnosis of asthma and documented spirometry with deployment to southwest Asia between 2006 and 2015 were identified. Of these, 76 individuals were identified with pre- and post-deployment spirometry. There was no significant change in the post-deployment forced expiratory volume at 1 second (% predicted), from 86.0 ± 14.8 to 87.6 ± 14.4 (P = .30). There was no significant change in post-deployment forced vital capacity (% predicted), from 93.8 ± 12.4 to 94.9 ± 12.1 (P = .42). The absolute change in forced expiratory volume at 1 second (L) after bronchodilator administration was decreased from pre-deployment to post-deployment (+0.31 ± 0.26 to +0.16 ± 0.23; P = .02). There was no significant post-deployment change in spirometry in this military population with asthma deployed to southwest Asia. These findings suggest that deployment itself is not associated with any short-term deleterious effect on post-deployment spirometric measures of lung function in many military personnel with asthma.

Development of the Siriraj Clinical Asthma Score

Acute asthmatic attack in children commonly occurs despite the introduction of effective controllers such as inhaled corticosteroids and leukotriene modifiers. Treatment of acute asthmatic attack requires proper evaluation of attack severity and appropriate selection of medical therapy. In children, measurement of lung function is difficult during acute attack and thus clinical asthma scoring may aid physician in making further decision regarding treatment and admission. We enrolled 70 children with acute asthmatic attack with age range from 1 to 12 years (mean ± SD = 51.5 ± 31.8 months) into the study. Twelve selected asthma severity items were assessed by 2 independent observers prior to administration of salbutamol nebulization (up to 3 doses at 20 minutes interval). Decision for further therapy and admission was made by emergency department physician. Three different scoring systems were constructed from items with best validity. Sensitivity, specificity and accuracy of these scores were assessed. Inter-rater reliability was assessed for each score. Review of previous scoring systems was also conducted and reported. Three severity items had poor validity, i.e., cyanosis, depressed cerebral function, and I:E ratio (p > 0.05). Three items had poor inter-rater reliability, i.e., breath sound quality, air entry, and I:E ratio. These items were omitted and three new clinical scores were constructed from the remaining items. Clinical scoring system comprised retractions, dyspnea, O2 saturation, respiratory rate and wheezing (rangeof score 0-10) gave the best accuracy and inter-rater variability and were chosen for clinical use-Siriraj Clinical Asthma Score (SCAS). A Clinical Asthma Score that is simple, relatively easy to administer and with good validity and variability is essential for treatment of acute asthma in children. Several good candidate scores have been introduced in the past. We described the development of the Siriraj Clinical Asthma Score (SCAS) in this report and reviewed the literature on the development of clinical asthma score for use in children.

Relationships of serum CC16 levels with smoking status and lung function in COPD

BackgroundThe club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown.MethodsUtilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation.ResultsThe study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22–0.57, Padj < 0.0001).ConclusionsSmoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.

Computed tomography-based body composition measures in COPD and their association with clinical outcomes: A systematic review.

BackgroundComputed tomography (CT) is commonly utilized in chronic obstructive pulmonary disease (COPD) for lung cancer screening and emphysema characterization. Computed tomography-morphometric analysis of body composition (muscle mass and adiposity) has gained increased recognition as a marker of disease severity and prognosis. This systematic review aimed to describe the CT-methodology used to assess body composition and identify the association of body composition measures and disease severity, health-related quality of life (HRQL), cardiometabolic risk factors, respiratory exacerbations, and survival in patients with COPD.MethodsSix databases were searched (inception-September 2021) for studies evaluating adult COPD patients using thoracic or abdominal CT-muscle or adiposity body composition measures. The systematic review was conducted in accordance with the PRISMA guidelines.ResultsTwenty eight articles were included with 15,431 COPD patients, across all GOLD stages with 77% males, age range (mean/median 59–78 years), and BMI range 19.8–29.3 kg/m2. There was heterogeneity in assessment of muscle mass and adiposity using thoracic (n = 22) and abdominal (n = 8) CT-scans, capturing different muscle groups, anatomic locations, and adiposity compartments (visceral, subcutaneous, and epicardial). Low muscle mass and increased adiposity were associated with increased COPD severity measures (lung function, exercise capacity, dyspnea) and lower HRQL, but were not consistent across studies. Increased visceral adiposity (n = 6) was associated with cardiovascular disease or risk factors (hypertension, hyperlipidemia, and diabetes). Low muscle CSA was prognostic of respiratory exacerbations or mortality in three of six studies, whereas the relationship with increased intermuscular adiposity and greater mortality was only observed in one of three studies.ConclusionThere was significant variability in CT-body composition measures. In several studies, low muscle mass was associated with increased disease severity and lower HRQL, whereas adiposity with cardiovascular disease/risk factors. Given the heterogeneity in body composition measures and clinical outcomes, the prognostic utility of CT-body composition in COPD requires further study.

Association of advanced paternal age with lung function at school age

BackgroundEpidemiological studies suggest that advanced paternal age impact offspring health, but its impact on respiratory health is unclear. This study aimed to investigate the association of paternal age with lung function and fraction of exhaled nitric oxide (FeNO) in children.MethodsWe analyzed data from 1330 single-born children (576 girls, 43.3%; mean age, 6.4 years), who participated in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort and received measurements of lung function and FeNO at 6-year follow-up visits. Covariate-adjusted regression analyses were applied.ResultsEvery 5-year increase in paternal age at birth was associated with 0.51% decrease in FEV1/FVC ratio (95% CI − 0.86 to − 0.15; p = 0.005) and 19.86 mL/s decrease in FEF75 (95% CI: − 34.07 to − 5.65; p = 0.006). Stratified analyses revealed that increasing paternal age at birth was associated with decreasing FEV1/FVC ratio and FEF75 only among children with prenatal exposure to environmental tobacco smoke (ETS) or not being breastfed. Sensitivity analyses using paternal age as a categorical variable found decreasing FEV1/FVC ratio and FEF75 in the groups of paternal age 35–39 and ≥ 40 years. There was no association of paternal age at birth with FeNO.ConclusionOur findings provide novel evidence linking advanced paternal age at birth with decreasing lung function in children at school age. Children with prenatal exposure to ETS or not being breastfed are more vulnerable to the adverse effect of advanced paternal age on childhood lung function. Further studies are warranted to confirm this novel adverse effect of advanced paternal age.

Reduced lung function predicts risk of incident type 2 diabetes: insights from a meta-analysis of prospective studies.

Epidemiological studies have repeatedly investigated the association between reduced pulmonary function and incident type 2 diabetes mellitus (T2DM). However, the results have been inconsistent. This meta-analysis aimed to clarify this association with prospective cohort studies. We searched PubMed, Web of Science (ISI), and Google Scholar for all studies (in English) reporting reduced lung function with a risk of T2DM. The measures of lung function included percentage of forced vital capacity for predicted values (FVC%pre), percentage of forced expiratory volume in the first second after expiration for predicted values (FEV1%pre) and FEV1-to-FVC ratio%. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects meta-analyses. A total of 5,480 incident T2DM patients among 88,799 individuals were identified from nine prospective cohort studies. Compared to the highest category of FVC%pre and FEV1%pre, the lowest category of FVC%pre and FEV1%pre were significantly associated with increased incident T2DM risk (FVC%pre: RR = 1.49, 95% CI: 1.39-1.59; FEV1%pre: RR = 1.52, 95% CI: 1.42-1.62). However, no significant relationship was found between the FEV1/FVC ratio and incident T2DM risk (RR = 1.01, 95% CI: 0.91-1.13). Current evidence suggests that restrictive rather than obstructive impairment of lung function is significantly associated with the incidence of T2DM. Further research is warranted to explore potential mediators of this relationship.

The impact of personal and outdoor temperature exposure during cold and warm seasons on lung function and respiratory symptoms in COPD.

RationaleChronic obstructive pulmonary disease (COPD) patients often report aggravated symptoms due to heat and cold, but few studies have formally evaluated this.MethodologyWe followed 30 Boston-based former smokers with COPD for four non-consecutive 30-day periods over 12 months. Personal and outdoor temperature exposure were measured using portable and Boston-area outdoor stationary monitors. Participants recorded daily morning lung function measurements as well as any worsening breathing (breathlessness, chest tightness, wheeze) and bronchitis symptoms (cough, sputum colour and amount) compared to baseline. Using linear and generalised linear mixed-effects models, we assessed associations between personal and outdoor temperature exposure (1–3-day moving averages) and lung function and symptoms, adjusting for humidity, smoking pack-years and demographics. We also stratified by warm and cold season.ResultsParticipants were on average 71.1±8.4 years old, with 54.4±30.7 pack-years of smoking. Each 5°C increase in personal temperature exposure was associated with 1.85 (95% CI 0.99–3.48) higher odds of worsening breathing symptoms. In the warm season, each 5°C increase in personal and outdoor temperature exposure was associated with 3.20 (95% CI 1.05–9.72) and 2.22 (95% CI 1.41–3.48) higher odds of worsening breathing symptoms, respectively. Each 5°C decrease in outdoor temperature was associated with 1.25 (95% CI 1.04–1.51) higher odds of worsening bronchitis symptoms. There were no associations between temperature and lung function.ConclusionsOur findings suggest that higher temperature, including outdoor exposure during the warm season and personal temperature exposure year-round, may worsen dyspnoea, while colder outdoor temperature may trigger cough and phlegm symptoms among COPD patients.

Differences in total lung capacity among Indians and Europeans

Background: Total lung capacity (TLC) is the volume of air in the lungs at the end of a maximal inhalation. TLC mainly depends on various factors/predictors such as height, age, gender, and ethnicity, and therefore, population-specific reference equations should be used. Currently, in India, we use the (European committee for coal and steel [ECCS], published in the year 1993) reference equation with no correction factor for TLC. It is recommended that the reference equation should be tested on a sample of local healthy participants, differences between the measured values and the predicted values are determined to see if the reference equation is a suitable/good fit for the population. Aim: The aim of this study was to compare the actual values of TLC from the healthy male and female volunteers from Pune city with the reference values obtained from the ECCS equations in these participants and determine the correction factor/percent differences between the mean values for different age and height groups. Design and Setting: A prospective, cross-sectional study of lung function measurements (TLC) by body plethysmography was carried out in a research center. Methodology: TLC was measured by Jaeger's Body Plethysmograph (model: Master scope) according to the recommendation of the American Thoracic Society's/European Respiratory Society's standards 2005 in a sample of 241 healthy nonsmoking volunteers (150 men and 82 women) aged 20–70 years, living in Pune city of Maharashtra, India. Statistical Analysis: The mean of actual TLC and the reference TLC were plotted against the different age groups and height groups and percentage difference was determined. Multiple linear regression was carried out to find the predictive equations for TLC parameter measured by the body plethysmography. Age, height, and weight were used as the predictors (independent variables) in the multiple regression analysis. Since sex is also a predictor of TLC, separate models were run for men and women. Results: There were statistically significant differences between the measured TLC and the reference TLC obtained from the ECCS equation in both males (5.05 L ± 0.69 vs. 6.3 L ± 0.50) and females (3.69 L ± 0.54 vs. 4.39 L ± 0.36), respectively. Males have higher TLC as compared to females of the same age and height. The mean of actual TLC and the reference TLC was plotted against different age groups and height groups, and percentage difference was determined. The percentage differences ranged from 17% to 21% in males and 13%–17% in females. Conclusion: The ECCS equation is not suitable for Pune population and may lead to misinterpretation of restrictive lung diseases and hyperinflation. A correction factor of 18.5% in males and 15% in females may be used for the ECCS equation for TLC in Pune population.

Lung Clearance Index to Detect Early Pulmonary Changes in Children with Sickle Cell Disease

<i>Objective:</i> Pulmonary complications including acute chest syndrome, are leading causes of sickle cell disease (SCD) related morbidity and mortality. Prior studies have shown that patients with pulmonary complications have evidence of pulmonary involvement reflected in lung functions trends as early as childhood. Spirometry is the current standard for measuring lung function. Growing evidence suggests that lung clearance index (LCI) which is a commonly reported parameter of multiple breath washout (MBW) tests, is more sensitive than spirometry measurements in the early identification of pulmonary changes in pediatric patients. The aim of our study was to determine if this relationship between LCI and spirometry existed within the pediatric sickle cell population. <i>Study Design: </i>This is a cross-sectional, retrospective study to compare LCI to spirometry measurements in children with SCD. Charts were reviewed of clinic encounters at Phoenix Children’s Hospital from March 1, 2013 – June 30, 2017. Spirometry and MBW measurements were collected from 23 patients between the ages of 5 years – 22 years. The MBW utilized sulfur hexafluoride (SF₆) as the tracer gas. Demographics and SCD variant (e.g. HbSS, HbSC, etc.) for each encounter were also collected. <i>Results: </i>Our results show that LCI correlates to FEV₁% predicted (Spearman’s coefficient -0.44, p = 0.003) and FEF_25-75% (Spearman’s coefficient -0.49, p <0.001) over time. Based on demographics, LCI is affected by weight (p = 0.046) but not age or height. When comparing LCI and FEV₁% predicted, abnormal LCI results were noted to occur even in the presence of normal FEV₁% predicted measurements. <i>Conclusions: </i>Our data support LCI correlating with spirometry measurements, but more studies are necessary to explore whether LCI can be used as a screening test to detect pulmonary changes in young children with SCD. Earlier monitoring of lung function will allow for preventative therapies and delayed progression of pulmonary dysfunction.

A historical overview of childhood asthma in southern Africa: Are we there yet?

Background The prevalence of asthma, the most common respiratory disease in children, has increased in many low- and middle-income countries (LMICs), particularly in Africa. Despite poor infrastructure and limited resources, researchers in southern Africa have sought to determine the prevalence of childhood asthma, with variable results reflecting actual differences as much as methodological limitations and biases. Objectives To collate and report findings from studies on the epidemiology of childhood asthma in southern Africa. Methods A review of the literature was undertaken. Results The prevalence of childhood asthma in southern Africa is variable but has increased over the last four decades, particularly in South Africa (3.17% to 21.29%). Methods used to assess the burden of asthma have been in the form of questionnaires, bronchial hypersensitivity provocation tests, lung function measurement and fractional exhaled nitric oxide (FENO). Conclusion The prevalence of childhood asthma is increasing in rural and urban areas in southern Africa. Research collaboration driven by a better understanding of the heterogeneous nature of asthma can improve challenges faced in evaluating the burden of asthma in African countries.

COVID-19 potentially causes long-term deterioration of lung function: a systematic review and meta-analysis

BACKGROUND The COVID-19 is an emerging disease that commonly involves respiratory complaints, including acute respiratory distress syndrome. The effect of COVID-19 on pulmonary function is still unclear and only based on sporadic reports with a small sample size. This study aimed to compile evidence on the pulmonary function of patients who have recovered from COVID-19.&#x0D; METHODS Literature searching was conducted in PubMed, Embase, Google Scholar, Scopus, Web of Sciences, and CINAHL. Any types of studies published before June 26, 2020 and reported lung function tests of post-COVID-19 patients were included. Articles reporting data from early hospitalization were excluded. The risk of bias was measured using tools developed by the Joanna Briggs Institute. Meta-analysis was done using a meta statistical package in R and presented in the random effects model.&#x0D; RESULTS 378 recovered COVID-19 patients in 7 studies were included. The lung function measurement periods were varied, ranging from 14 days after hospitalization to 10 weeks after receiving rehabilitation. Meta-analyses found that the pooled mean of diffusion capacity of carbon monoxide in recovered COVID-19 patients was lower than 80% predicted, whereas the other parameters were normal. The forced vital capacity and total lung capacity showing restrictive lung disorders were significantly lower in the severe COVID-19 survivors.&#x0D; CONCLUSIONS COVID-19 has a negative impact on lung function for at least several weeks in the recovery period. Diffusion and restrictive problems could be the main long-term consequences of COVID-19.

ERS/ATS technical standard on interpretive strategies for routine lung function tests.

Appropriate interpretation of pulmonary function tests (PFTs) involves the classification of observed values as within/outside the normal range based on a reference population of healthy individuals, integrating knowledge of physiological determinants of test results into functional classifications and integrating patterns with other clinical data to estimate prognosis. In 2005, the American Thoracic Society (ATS) and European Respiratory Society (ERS) jointly adopted technical standards for the interpretation of PFTs. We aimed to update the 2005 recommendations and incorporate evidence from recent literature to establish new standards for PFT interpretation. This technical standards document was developed by an international joint Task Force, appointed by the ERS/ATS with multidisciplinary expertise in conducting and interpreting PFTs and developing international standards. A comprehensive literature review was conducted and published evidence was reviewed. Recommendations for the choice of reference equations and limits of normal of the healthy population to identify individuals with unusually low or high results are discussed. Interpretation strategies for bronchodilator responsiveness testing, limits of natural changes over time and severity are also updated. Interpretation of measurements made by spirometry, lung volumes and gas transfer are described as they relate to underlying pathophysiology with updated classification protocols of common impairments. Interpretation of PFTs must be complemented with clinical expertise and consideration of the inherent biological variability of the test and the uncertainty of the test result to ensure appropriate interpretation of an individual's lung function measurements.

A stochastic mixed effects model to assess treatment effects and fluctuations in home‐measured peak expiratory flow and the association with exacerbation risk in asthma

Home‐based measures of lung function, inflammation, symptoms, and medication use are frequently collected in respiratory clinical trials. However, new statistical approaches are needed to make better use of the information contained in these data‐rich variables. In this work, we use data from two phase III asthma clinical trials demonstrating the benefit of benralizumab treatment to develop a novel longitudinal mixed effects model of peak expiratory flow (PEF), a lung function measure easily captured at home using a hand‐held device. The model is based on an extension of the mixed effects modeling framework to incorporate stochastic differential equations and allows for quantification of several statistical properties of a patient's PEF data: the longitudinal trend, long‐term fluctuations, and day‐to‐day variability. These properties are compared between treatment groups and related to a patient's exacerbation risk using a repeated time‐to‐event model. The mixed effects model adequately described the observed data from the two clinical trials, and model parameters were accurately estimated. Benralizumab treatment was shown to improve a patient's average PEF level and reduce long‐term fluctuations. Both of these effects were shown to be associated with a lower exacerbation risk. The day‐to‐day variability was neither significantly affected by treatment nor associated with exacerbation risk. Our work shows the potential of a stochastic model‐based analysis of home‐based lung function measures to support better estimation and understanding of treatment effects and disease stability. The proposed analysis can serve as a complement to descriptive statistics of home‐based measures in the reporting of respiratory clinical trials.