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RATIONALE: Obstructive sleep apnea is highly prevalent in children with asthma, particularly in obese children. The sleep related breathing disorder screening questionnaire has low screening accuracy for obstructive sleep apnea in children with asthma. Our goal was to identify the questions on the sleep related breathing disorder survey associated with obstructive sleep apnea in children with asthma. METHODS: Participants completed the survey, underwent polysomnography and their body mass index z-score was measured. Participants with survey scores above 0.33 were considered high risk for obstructive sleep apnea and those with an apnea hypopnea index ≥ 2 events/hour classified as having obstructive sleep apnea. Logistic regression was used to examine the association of each survey question and obstructive sleep apnea. Positive and negative predictive values were calculated to estimate screening accuracy. RESULTS: The prevalence of obstructive sleep apnea was 40% in our sample (n=136). Loud snoring, morning dry mouth and being overweight were the questions associated with obstructive sleep apnea. A combined model of loud snoring, morning dry mouth and being overweight had positive and negative predictive values of 57.4% and 81.0% respectively, while the composite survey score had positive and negative predictive values of 51.0% and 65.5%. Body mass index z-score had positive and negative predictive values of 76.3% and 72.2%. CONCLUSIONS: The body mass index z-score is useful for obstructive sleep apnea screening in children with asthma and should be applied routinely given its simplicity and concerns that obstructive sleep apnea may contribute to asthma morbidity.

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin’s protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (−0.92%; 95% confidence interval [CI], −1.7% to −0.14%; P = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.

OBJECTIVE: Black children and children from low-income communities are disproportionately affected by asthma, attributed partly to pollution exposure. Air purifiers reduce indoor air pollution and improve asthma symptoms in children. In order to implement air purifier interventions, an understanding of patterns of use and potential barriers is necessary. METHODS: In a home intervention study, 127 children with asthma living in Baltimore were randomized to receive two active or two placebo air purifiers. The 16-week study period included: baseline clinic visit, home visit for air purifier installation (active or placebo) with instruction to use the high or turbo settings, and electronic adherence monitoring of air purifiers. Determinants of adherence were identified using linear regression models. RESULTS: Air purifiers were used 80% of the time, and participants demonstrated adherence to high or turbo settings for 60% of the time. In an adjusted model, season was the major determinant of air purifier adherence, with 21% lower use in the winter (p=0.025) attributed to the cold draft generated by the machine. CONCLUSION: In a clinical trial with electronic adherence monitoring, air purifier use was high and participants were adherent to use of high or turbo settings the majority of the time. Addressing practical barriers to consistent use, such as draft during the winter, in addition to financial barriers may improve air purifier adherence among children with asthma living in low-income, urban households.

A workshop “Electronic Health Records and Pulmonary Function Data: Developing an Interoperability Roadmap” was held at the American Thoracic Society 2019 International Conference. “Interoperability” is defined as is the ability of different information-technology systems and software applications to directly communicate, exchange data, and use the information that has been exchanged. At present, pulmonary function test (PFT) equipment is not required to be interoperable with other clinical data systems, including electronic health records (EHRs). For this workshop, we assembled a diverse group of experts and stakeholders, including representatives from patient-advocacy groups, adult and pediatric general and pulmonary medicine, informatics, government and healthcare organizations, pulmonary function laboratories, and EHR and PFT equipment and software companies. The participants were tasked with two overarching Aobjectives: 1) identifying the key obstacles to achieving interoperability of PFT systems and the EHR and 2) recommending solutions to the identified obstacles. Successful interoperability of PFT data with the EHR impacts the full scope of individual patient health and clinical care, population health, and research. The existing EHR–PFT device platforms lack sufficient data standardization to promote interoperability. Cost is a major obstacle to PFT–EHR interoperability, and incentives are insufficient to justify the needed investment. The current vendor–EHR system lacks sufficient flexibility, thereby impeding interoperability. To advance the goal of achieving interoperability, next steps include identifying and standardizing priority PFT data elements. To increase the motivation of stakeholders to invest in this effort, it is necessary to demonstrate the benefits of PFT interoperability across patient care and population health.

To determine whether school infrastructure is associated with health and academic outcomes among elementary school children with asthma.We conducted a retrospective cohort study of linked medical, academic, and facilities data from a large mid-Atlantic school district of the United States. All K-5 students with asthma who were enrolled under the state's Children's Health Insurance Program were included. We estimated associations of the infrastructure quality of the student's school, as assessed by an engineering firm in Summer 2011 and represented by the Facility Condition Index (FCI), with asthma health outcomes, absenteeism, and standardized test scores in math and reading in the two academic years thereafter.6,558 students were identified, the majority non-Hispanic Black, across 130 schools. Most schools (97/130, 75%) were in very poor or worse condition. In cluster-adjusted models accounting for demographics, grade, school-specific area deprivation, and inhaled corticosteroid use, a one standard deviation increase in FCI, corresponding to greater infrastructure deficiency, was associated with higher rates of asthma-related hospitalizations (incidence rate ratio [IRR] 1.16; 95% confidence interval [CI] 1.03, 1.32), more absenteeism (IRR 1.05; 95% CI 1.01, 1.08), and lower scores in math (mean difference [MD] -3.3; 95% CI -5.5, -1.2) and reading (MD -3.0; 95% CI -5.1, -0.9). There were no differences in rates of asthma-related emergency visits or steroid prescriptions.Children with asthma attending schools with poorer infrastructure had worse health and academic outcomes. Public policy emphasizing reinvestment in school infrastructure may be a potential means of addressing asthma disparities.

Purpose of review Disorders of glucose metabolism, including insulin resistance, prediabetes, and diabetes, have been identified as risk factors for worsened asthma. This review summarizes emerging evidence for their role as modifiable risk factors in asthma, including the potential benefit of diabetes medications on asthma outcomes. Recent findings Experimental studies show that hyperinsulinemia associated with insulin resistance is associated with airway smooth muscle proliferation and promotes contractility. Epidemiologic studies have identified a higher prevalence of glycemic dysfunction among those with severe and uncontrolled asthma, and longitudinal studies have associated prediabetes and diabetes with higher risk of asthma exacerbations. The potential benefits of thiazolidinediones (TZDs), glucagon-like peptide-1 agonists, and metformin being investigated in asthma, but thus far interventional studies of TZDs have reported null results. On the contrary, observational studies have inconsistently controlled for relevant confounders which leaves conclusions vulnerable to misattribution of relationships due to corelated metabolic disorders, including dyslipidemia. Summary Developing evidence suggests that disorders of glucose metabolism may be associated with worsening asthma. However, these conditions arise within a network of obesity-related metabolic diseases that may themselves worsen asthma. Few interventional trials have not identified a benefit, but data have been limited. Additional research is needed to define the potential independent impact of disorders of glucose metabolism in asthma.

Children spend the majority of their time indoors, and a substantial portion of this time in the school environment. Air pollution has been shown to adversely impact lung development and has effects that extend beyond respiratory health. The goal of this study was to evaluate the indoor environment in public schools in the context of an ongoing urban renovation program to investigate the impact of school building renovation and replacement on indoor air quality. Indoor air quality (CO2, PM2.5, CO, and temperature) was assessed for two weeks during fall, winter, and spring seasons in 29 urban public schools between December 2015 and March 2020. Seven schools had pre- and post-renovation data available. Linear mixed models were used to examine changes in air quality outcomes by renovation status in the seven schools with pre- and post-renovation data. Prior to renovation, indoor CO measurements were within World Health Organization (WHO) guidelines, and indoor PM2.5 measurements rarely exceeded them. Within the seven schools with pre- and post-renovation data, over 30% of indoor CO2 measurements and over 50% of indoor temperatures exceeded recommended guidelines from the American Society of Heating, Refrigerating, and Air Conditioning Engineers. Following renovation, 10% of indoor CO2 measurements and 28% of indoor temperatures fell outside of the recommended ranges. Linear mixed models showed significant improvement in CO2, indoor PM2.5, and CO following school renovation. Even among schools that generally met recommendations on key guidelines, school renovation improved the indoor air quality. Our findings suggest that school renovation may benefit communities of children, particularly those in low-income areas with aging school infrastructure, through improvements in the indoor environment.

Background Diabetes is associated with worse asthma morbidity. Metformin, which treats diabetes, may have a role among patients with asthma and glycemic dysfunction. Objective To determine the association between metformin use and asthma exacerbations among patients with diabetes. Methods We queried the Johns Hopkins electronic health record from April 1, 2013, to May 31, 2018. Adults with asthma and diabetes were followed from first hemoglobin A1c (HbA1c) test to an asthma-related systemic corticosteroid prescription, emergency department (ED) visit, or hospitalization. Multivariable Cox models estimated time to each outcome associated with metformin use, modeled as either time-invariant (status at HbA1c testing) or time-dependent (based on fill data). Mediation of results by HbA1c was assessed. Sensitivity analysis was performed by propensity score matching. Results The cohort comprised 1749 adults with asthma and diabetes. Metformin use at entry was associated with a lower hazard of asthma-related ED visits (adjusted hazard ratio [aHR], 0.40; 95% CI, 0.22-0.75) but not steroid prescription (aHR, 0.89; 95% CI, 0.70-1.13) or hospitalization (aHR, 0.38; 95% CI, 0.13-1.12). HbA1c did not mediate the association with ED visits. With metformin exposure modeled as time-dependent, metformin use was additionally associated with lower hazard of asthma-related hospitalization (aHR, 0.30; 95% CI, 0.09-0.93). Results were consistent within a subcohort of 698 metformin users matched 1:1 to nonusers by propensity score. Conclusions Metformin use, independent of glycemic control and obesity, was associated with lower hazard of asthma-related ED visits and hospitalizations. Metformin may have benefit in patients with asthma and glycemic dysfunction.

CONTEXT Secondhand smoke exposure (SHSe) affects up to half of all children in the United States. Many studies have identified factors associated with in-home SHSe, but few have contrasted these factors between households with and without residential smokers. In the latter case, exposure occurs from only external sources that enter the home, such as visitors or environmental incursion. OBJECTIVE Among children with SHSe at home, to examine demographic and psychosocial differences between households with and without residential smokers. DESIGN Baseline analysis of an observational cohort. SETTING Baltimore City, Maryland. PARTICIPANTS A total of 157 children with asthma, aged 5 to 12 years. MEASURES At-home airborne nicotine, caregiver-reported depression, asthma-related quality of life, functional social support, and demographics. Univariable comparisons were performed between SHS-exposed households with and without residential smokers. Multivariable logistic regression models were fit to examine associations between measured factors and absence of residential smokers. RESULTS Children (78.3%) had at-home SHSe. Of these, 40.7% lived in households without residential smokers. Compared with households with residential smokers, these caregivers endorsed stronger beliefs in SHS harms and also worse functional social support and asthma-related stress, despite no differences in asthma morbidity. In adjusted models, SHS-exposed children with caregivers in the lowest tertile of functional social support (adjusted odds ratio, 3.50; 95% confidence interval, 1.12-10.99), asthma-related quality of life (2.90; 1.06-7.95), and those living alone (5.28; 1.26-22.15) had at least twice higher odds of having exclusively external SHSe than the highest tertile (P trends < .05). CONCLUSIONS In-home SHS exposure remains alarmingly high in urban environments. However, a substantial proportion of this exposure appears to be occurring only from external sources that enter the home. Caregivers in these homes had higher desire but lower agency to avoid SHSe, driven by lack of functional support and physical isolation. Public policies targeting these factors may help remediate exposure in this especially vulnerable population.

BACKGROUND: Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION: What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS: This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV(1), FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS: TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION: TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.

BackgroundObese children with asthma are more vulnerable to air pollution, especially fine particulate matter (PM2.5), but reasons are poorly understood. We hypothesised that differences in breathing patterns (tidal volume, respiratory rate and minute ventilation) due to elevated body mass index (BMI) may contribute to this finding.ObjectiveTo investigate the association of BMI with breathing patterns and deposition of inhaled PM2.5.MethodsBaseline data from a prospective study of children with asthma were analysed (n=174). Tidal breathing was measured by a pitot-tube flowmeter, from which tidal volume, respiratory rate and minute ventilation were obtained. The association of BMI z-score with breathing patterns was estimated in a multivariable model adjusted for age, height, race, sex and asthma severity. A particle dosimetry model simulated PM2.5 lung deposition based on BMI-associated changes in breathing patterns.ResultsHigher BMI was associated with higher tidal volume (adjusted mean difference (aMD) between obese and normal-range BMI of 25 mL, 95% CI 5–45 mL) and minute ventilation (aMD 453 mL·min−1, 95% CI 123–784 mL·min−1). Higher tidal volumes caused higher fractional deposition of PM2.5 in the lung, driven by greater alveolar deposition. This translated into obese participants having greater per-breath retention of inhaled PM2.5 (aMD in alveolar deposition fraction of 3.4%, 95% CI 1.3–5.5%), leading to worse PM2.5 deposition rates.ConclusionsObese children with asthma breathe at higher tidal volumes that may increase the efficiency of PM2.5 deposition in the lung. This finding may partially explain why obese children with asthma exhibit greater sensitivity to air pollution.

Additional file 1: Table S1. Baseline characteristics of included participants by asthma-COPD overlap status (n=3969). Table S2. Adjusted mean difference (95% confidence interval) in change of secondary outcomes from baseline to 5-year follow-up between metformin users and non-users. Table S3. Adjusted mean difference (95% confidence interval) comparing metformin users to non-users for cross-sectional secondary outcomes including participants without follow-up data. Figure S1. STROBE diagram of cohort derivation. Figure S2. Incidence rate ratio (95% confidence interval) comparing metformin users to non-users for exacerbations stratified by alternative alternative asthma-COPD overlap (ACO) definitions (n=3969)

Background Metformin is associated with improved respiratory outcomes in asthma; however, metformin in COPD and asthma-COPD overlap (ACO) remains unexplored. Objective To determine the association between metformin use and respiratory outcomes in COPD and ACO. Study design and methods Participants with COPD (FEV1/FVC Results Among participants with ACO, metformin use was associated with lower rate of total (adjusted incidence rate ratio [aIRR] 0.3; 95% confidence interval [95%CI] 0.11, 0.77) and severe exacerbations (aIRR 0.29; 95%CI 0.10, 0.89). Among participants with COPD alone, there was no association between metformin use with total (aIRR 0.98; 95%CI 0.62, 1.5) or severe exacerbations (aIRR 1.3; 95% CI 0.68, 2.4) (p-interaction Conclusions Metformin use was associated with fewer respiratory exacerbations and improved quality of life among individuals with ACO but not COPD alone. Results suggest a potential role for metformin in ACO which requires further prospective study. Trial Registry: NCT00608764

Rationale: Diabetes and metabolic syndrome have been associated with worsened asthma control. Metformin improves insulin resistance and metabolic function. Experimental studies suggest that metformin may improve pathologic features of asthma, but evidence of clinical benefit is limited. Objectives: To determine if treatment with metformin in a cohort of individuals with asthma and diabetes is associated with lower risk of asthma exacerbation. Methods: A 6-year retrospective cohort of individuals over age 18 with asthma and diabetes was assembled from a national administrative claims database. New users of metformin were matched to nonusers by propensity score on the basis of demographic, comorbidity, and medication-use characteristics. An exacerbation was defined as an asthma-related hospitalization, emergency department visit, or filling of a systemic corticosteroid prescription within 14 days of an asthma-related ambulatory visit. Cox proportional hazards estimated the change in hazard of asthma exacerbation associated with metformin initiation. Results: In a cohort of 23,920 individuals with asthma and diabetes, metformin initiation was associated with lower hazard of asthma exacerbation (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.98), driven by lower hazards of asthma-related emergency department visits (HR, 0.81; 95% CI, 0.74–0.88) and hospitalization (HR, 0.67; 95% CI, 0.50–0.91), without differences in corticosteroid use (HR, 0.96; 95% CI, 0.86–1.03). Conclusions: In an administrative cohort of individuals with asthma and diabetes, metformin initiation was associated with a lower hazard of asthma-related emergency department visits and hospitalizations. These findings suggest a possible benefit of metformin in more severe asthma exacerbations. Investigation within cohorts with more detailed participant characterization is necessary.

BACKGROUND: Insulin resistance and metabolic dysfunction have been associated with asthma risk and asthma severity. OBJECTIVE: To examine the association between glycated hemoglobin A1c (HbA1c), asthma-related hospitalizations, and lung function measures among adults in the United Kingdom (U.K.). METHODS: Cross-sectional study of 47,606 adults aged 40 to 69 years old who participated in the UK Biobank and had asthma but no diagnosis of diabetes mellitus. HbA1c level was analyzed as a continuous measure and also categorized as normal (

An obesity paradox in chronic obstructive pulmonary disease (COPD), whereby overweight/obese individuals have improved survival, has been well-described. These studies have generally included smokers. It is unknown whether the paradox exists in individuals with COPD arising from factors other than smoking. Nonsmoking COPD is understudied yet represents some 25%–45% of the disease worldwide. To determine whether the obesity paradox differs between ever- and never-smokers with COPD, 1,723 adult participants with this condition were examined from 2 iterations of the National Health and Nutrition Examination Survey (1988–1994, 2007–2010), with mortality outcomes followed through December 2011. Using Cox proportional hazards models, adjusted for sociodemographic factors, lung function, and survey cycle, ever/never-smoking was found to modify the association between body mass index and hazard of death. Compared with normal-weight participants, overweight/obese participants had lower hazard of death among ever-smokers (for overweight, adjusted hazard ratio (aHR) = 0.56, 95% confidence interval (CI): 0.43, 0.74; for obesity, aHR = 0.66, 95% CI: 0.48, 0.92), but never-smokers did not (overweight, aHR = 1.41, 95% CI: 0.66, 3.03; obesity, aHR = 1.29, 95% CI: 0.48, 3.48). An obesity paradox appeared to be absent among never-smokers with COPD. This, to our knowledge, novel finding might be explained by pathophysiological differences between smoking-related and nonsmoking COPD or by smoking-associated methodological biases.

BACKGROUND: Metabolic dysfunction may contribute to worsened asthma in obesity. The relationship between pre-diabetes and diabetes, metabolic conditions more common in obesity, with asthma outcomes is not well-characterized. OBJECTIVE: We sought to determine the association between pre-diabetes/diabetes and asthma exacerbations in an obese asthma cohort. METHODS: A retrospective cohort of US adults with obese asthma, age 18–64, was created from a claims-based health services database spanning 2010–2015. Individuals with a hemoglobin A1c (HbA1c) measurement were identified, categorized as within normal (

Pulmonary function testing has a rich and diverse history. Since the time of ancient Greece, we have endeavored to understand the processes that regulate our breathing in health and disease. To augment this understanding, there are many extensive published histories of pulmonary function and physiology, and the reader is advised to seek out further details as listed in the Selected References. Within the confines of the present book, this chapter will focus on selected highlights relevant to clinical pulmonary function testing, through which we hope that the reader can gain a deeper understanding of the different tests as each is done today.

In two observational cohorts of inner-city children with asthma, secondhand smoke exposure was associated with worsened symptoms in overweight/obese compared to normal weight children, suggesting that elevated BMI may increase susceptibility to secondhand smoke, a common indoor pollutant.