Pretreatment Alveolar Nitric Oxide Levels Predict Improvement of Pulmonary Function 1 Year Following Anti-Asthma Treatments in Patients with Inhaled Corticosteroid-Naïve Asthma

<b><i>Introduction:</i></b> Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV₁) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. <b><i>Methods:</i></b> We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β₂-agonists (ICS/LABA) was initiated. FEV₁ and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV₁ (ΔFEV₁) were analyzed. Patients with a ΔFEV₁ &#x3c;–20 mL were defined as “poor-responders.” <b><i>Results:</i></b> FEV₁, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV₁ was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV₁ on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (<i>p</i> = 0.009). <b><i>Conclusion:</i></b> Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV₁.

Airway to Lung Volume Ratio on CT is Associated with Pulmonary Function Transition from Obstructive to Restrictive Pattern in Obesity

Background: Obesity is associated with excessive airway collapse and reduced lung volume; it is unknown whether it affects airway-lung interactions. We sought to compare the airway tree to lung volume ratio, assessed by CT, in obese individuals with and without ventilation disorders.Methods: Participants underwent inspiratory chest CT and pulmonary function. The percentage ratio of the whole airway tree to lung volume, automatically segmented via deep learning, was defined as CT airway volume percent (AWV%). Total airway count (TAC), airway wall area percent (WA%), and other CT indexes were also measured. Results: We evaluated 88 participants including adolescents(age: 14-18, n= 12) and adults (age: 19-25, n= 17; age: 26-35, n= 39; age> 35, n= 20). Obese adolescents had higher forced vital capacity (FVC) (P = 0.001) and lower AWV% (P = 0.008) than obese adults (age >35). Among obese adults, participants with restrictive disorders had larger AWV% (P < 0.001) and those with obstructive disorders showed smaller AWV% (P < 0.001) compared to participants with normal ventilation. AWV% was positively correlated with age and forced expiratory volume in 1 second (FEV1)/FVC and adversely related to FVC (P< 0.05 for all), and in multivariate models, AWV% independently predicted FEV1/FVC (R2 = 0.49, P < 0.001) and FVC (R2 = 0.60, P < 0.001).Conclusion: Transitions in lung function patterns between obese adolescents and adults are associated with airway to lung ratios. The obesity-induced disproportion between the airway tree and lung volume may adversely affect and complicate lung ventilation.

The Effects of Exercise Therapy Moderated by Sex in Rehabilitation of COVID-19

BackgroundPulmonary rehabilitation serves as a key component in the recovery of COVID-19 and standardized exercise therapy programs in pulmonary rehabilitation have been shown to significantly improve physical performance and lung function parameters in post-acute COVID-19 patients. However, it has not been investigated if these positive effects are equally beneficial for both sexes, especially considering a more severe physical impact of COVID-19 in men when compared to women. Therefore, the purpose of this study was to analyze outcomes of a pulmonary rehabilitation program with respect to sex differences, in order to identify sex-specific pulmonary rehabilitation requirements.MethodsData of 233 patients (40.4% females) were analyzed before and after a three-week standardized pulmonary rehabilitation program. Patients were admitted to rehabilitation due to post-acute COVID-19 illness and staged using the COVID-19 Severity Scale by Huang et al. (2021). Lung function parameters were assessed as part of the clinical routine using spirometry (ICmax, maximal inspiratory capacity) and body plethysmography (FVC, forced vital capacity; FEV1, forced expiratory volume in the first second) and functional exercise capacity was measured by the Six-Minute Walk Test (6MWT). For the comparison of lung function and walking parameters by sex, Welch-ANOVA was used, as results of Levene's test suggested significant heteroscedasticity regarding the investigated parameters (p > 0.05). When comparing post-treatment 6MWT, FEV1 and FCV to corresponding reference values, paired t-tests were used.ResultsAt post-rehabilitation, ICmax, FVC, FEV1 and 6MWT has been improved in both sexes. Females showed a significantly smaller improvement in FEV1 and ICmax (F = 5.86, ω2 = .02; p < 0.05) than males. There was no statistically significant difference in FVC and 6MWT performance improvements between men and women. After the rehabilitation stay, females made greater progress towards reference values of 6MWT (T(231) = -3.04; p < 0.01) and FEV1 (T(231) = 2.83; p < 0.01) than males.ConclusionsSex differences in the improvement of lung function parameters seem to exist when completing a three-week pulmonary rehabilitation program and should be considered when personalizing standardized exercise therapies in pulmonary rehabilitation.Trial registrationthis study was registered in the German Clinical Trials Register (DRKS00026936) on 2021/10/19.

Long-term Improvement of Air Quality Associated with Lung Function Benefits in Chinese Young Adults: A Quasi-experiment Cohort Study

Background: Long-term exposure to air pollution is associated with lung function impairment. However, whether long-term improvements in air quality could improve lung function is unclear.<br />Methods: We conducted a prospective quasi-experiment cohort study with 1731 college students in Shandong, China from September 2019 to September 2020, covering COVID-19 lockdown period. Data on PM2.5, PM10, NO2 and SO2 concentrations were obtained from China Environmental Monitoring Station. The concentration of O3 was obtained from Tracking Air Pollution in China. Lung function indicators included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and forced expiratory flow at 50% of FVC (FEF50%). Linear mixed-effects model was used to examine the associations between the change of air pollutants’ concentrations and the change of lung functions. We also conducted stratified analysis by sex.<br />Results: Compared with 2019, the mean FVC, FEV1 and FEF50% were elevated by 414.4ml, 321.5ml, and 28.4ml respectively in 2020. Every 5μg/m3 decrease in annual average PM2.5 concentrations was associated with 36.0ml [95% confidence interval (CI):6.0, 66.0ml], 46.1ml (95% CI:16.7, 75.5ml), and 124.2ml/s (95% CI:69.5, 178.9ml/s) increment in the FVC, FEV1, and FEF50%, respectively. Similar associations were found for PM10. There was no significant effect difference between male and female.<br />Conclusions: Long-term improvement of air quality can improve lung function among young adults. Stricter policies on improving air quality are needed to protect human health.<br />Funding: Taishan Scholar Program

A study of correlation of pulmonary function test in patients with metabolic syndrome with different components of metabolic syndrome

Background: The increasing incidence of metabolic syndrome has been on the rise especially in urban population and leading to increased risk of cardiovascular disease (CVD) and diabetes mellitus. It has been associated with impairment of pulmonary functions. However, there is limited data regarding the association with individual components of metabolic syndrome and overall effect on components of pulmonary functions.Methods: This is a cross sectional study consisting of 50 subjects with metabolic syndrome. All the subjects underwent pulmonary function tests and the association between different components of metabolic syndrome and pulmonary function were examined using unpaired t-test and Pearson’s partial correlation coefficient. This data was analysed by using statistical package for the social sciences (SPSS) version 12.0.Results: In females, moderate negative significant correlation was seen between forced vital capacity (FVC) and systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), triglyceride (TG), waist circumference (WC) and body mass index (BMI) whereas positive weak non-significant correlation was seen between FVC and high density lipoprotein cholesterol (HDLC), while no such relation was found with forced expiratory volume in one second (FEV1). In males, negative, moderate significant correlation was seen between FVC and FBS whereas strong, positive, significant correlation was seen between FVC and WC; between FVC and BMI. Negative, moderate, significant correlation was seen between FEV1 and WC; between FEV1 and BMI.Conclusions: Our study concluded that there was a significant impact of FBS and WC on decreasing FVC on both genders with minimally significant impact of other components of metabolic syndrome on FVC with no effect on FEV1 hence indicating a restrictive pattern of pulmonary function derangement. Hence, further studies with larger sample size is needed to confirm whether there are direct or indirect mechanisms through which insulin resistance could affect pulmonary function.

How do growth and nutrition explain social inequalities in lung function in children with cystic fibrosis? A longitudinal mediation analysis using interventional disparity effects with time-varying mediators and intermediate confounders.

Background Deprivation is associated with poorer growth, worse lung function and shorter life expectancy in children with cystic fibrosis (CF). While early growth is associated with lung function when first measured at around age 6, it is unclear whether improving early growth in the most disadvantaged children would reduce inequalities in lung function. Methods We used data from children born 2000-2010 and followed up to 2016 in the UK CF Registry. To estimate the association between deprivation and lung function at around age six, and the causal contribution of early weight trajectories, we extended the mediation analysis approach based on interventional disparity effects to the setting of a longitudinally measured mediator. We adjusted for baseline confounding by sex, birthyear and genotype and accounted for time-varying intermediate confounding by lung infection. Results 853 children were included in the study, including 165 and 172 children from the least and most deprived population quintiles, respectively. The average difference in lung function between the least and most deprived quintile of children, was 4.51 percent of predicted forced expiratory volume in one second (95% CI: 1.08-7.93). We estimated this would be reduced to 3.97 percentage points (95% CI: 0.57-7.38) if early weight trajectories in the most deprived children were shifted to the distribution observed in the least disadvantaged children. Conclusion Socio-economic conditions are strongly associated with lung function for children with CF which we estimated would only be marginally reduced if early weight trajectories could be improved for the most disadvantaged children.

Predictive Factors for and Complications of Bronchiectasis in Common Variable Immunodeficiency Disorders

Bronchiectasis is a frequent complication of common variable immunodeficiency disorders (CVID). In a cohort of patients with CVID, we sought to identify predictors of bronchiectasis. Secondly, we sought to describe the impact of bronchiectasis on lung function, infection risk, and quality of life. We conducted an observational cohort study of 110 patients with CVID and an available pulmonary computed tomography scan. The prevalence of bronchiectasis was 53%, with most of these patients (54%) having mild disease. Patients with bronchiectasis had lower median serum immunoglobulin (Ig) concentrations, especially long-term IgM (0 vs 0.25 g/l; p < 0.01) and pre-treatment IgG (1.3 vs 3.7 g/l; p < 0.01). CVID patients with bronchiectasis had worse forced expiratory volume in one second (2.10 vs 2.99 l; p < 0.01) and an annual decline in forced expiratory volume in one second of 25 ml/year (vs 8 ml/year in patients without bronchiectasis; p = 0.01). Patients with bronchiectasis also reported more annual respiratory tract infections (1.77 vs 1.25 infections/year, p = 0.04) and a poorer quality of life (26 vs 14 points in the St George’s Respiratory Questionnaire; p = 0.02). Low serum immunoglobulin M concentration identifies patients at risk for bronchiectasis in CVID and may play a role in pathogenesis. Bronchiectasis is relevant because it is associated with frequent respiratory tract infections, poorer lung function, a greater rate of lung function decline, and a lower quality of life.

SPECT/CT versus planar imaging to determine treatment strategy for non-small-cell lung cancer: a cost–effectiveness analysis

Aim: SPECT/CT has been found to improve predicted postoperative forced expiratory volume in one second (ppoFEV1) assessments in patients with non-small-cell lung cancer (NSCLC). Methods: An economic simulation was developed comparing the cost–effectiveness of SPECT/CT versus planar scintigraphy for a US payer. Clinical outcomes and cost data were obtained through review of the published literature. Results: SPECT/CT increased the accuracy ppoFEV1 assessment, changing the therapeutic decision for 1.3% of nonsurgical patients to a surgical option, while 3.3% of surgical patients shifted to more aggressive procedures. SPECT/CT led to an expected cost of $4694 per life year gained, well below typical thresholds. Conclusion: SPECT/CT resulted in substantially improved health outcomes and was found to be highly cost-effective.

Interplay Between Thyroid Hormone Status and Pulmonary Hypertension in Graves’ Disease: Relevance of the Assessment in Thyrotoxic and Euthyroid Patients

BackgroundGraves’ disease (GD) is the most common cause of hyperthyroidism and can cause cardiac changes, such as pulmonary hypertension.MethodsThis is a prospective study in which we obtained demographic, clinical, laboratory data and characteristics of the GD, in addition to investigating cardiorespiratory function, focusing on the detection of pulmonary hypertension. Patients were separated into two groups: thyrotoxicosis and euthyroidism. Ninety patients with GD of both sexes, over 18 years of age, were included. The cardiorespiratory assessment included an echocardiographic evaluation, a questionnaire of specific symptoms, spirometry and a six-minute walk test.ResultsThe hyperthyroid group included 42 patients (47.73%) and the euthyroid group 46 patients (52.27%); 78 were women (86.67%). The prevalence of pulmonary hypertension between the hyperthyroidism (48.57%) and the euthyroidism (29.41%) groups was not different. Free thyroxine levels (FT4) (OR 1.266), higher left atrium volume (OR 1.113) and right ventricle diameter were associated with pulmonary hypertension. A direct correlation between FT4 with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as also an inverse correlation between initial oxygen saturation (SpO2) with diagnostic time and drop SpO2 with the ratio between the diastolic velocity E of the mitral flow and the diastolic velocity of the mitral ring (E/e’) were observed in the euthyroid group. An inverse correlation between FT4 levels with walked distance as % of predicted value, and a direct correlation between E/e’ ratio and walked distance as % of predicted value were observed in the hyperthyroid group.ConclusionWe emphasize the importance of a cardiorespiratory reassessment in GD, even after a long-term control of the thyrotoxic state, as we demonstrate that about 30% of these patients remain with PH and are subject to specific treatment.

Diverging trends of respiratory allergies and eczema in Greek schoolchildren: Six surveys during 1991‐2018

Background: The prevalence of childhood asthma, rhinoconjunctivitis, and eczema in the city of Patras, Greece, has been followed in four consecutive surveys since 1991. After a continuous rise in the prevalence of all three of these disorders, a plateau was reached for asthma between 2003 and 2008, whereas the prevalence of rhinoconjunctivitis and eczema continued to increase. Objective: To investigate these trends in the same population into the following decade. Methods: We repeated two methodologically identical cross-sectional parental questionnaire surveys in 2013 and 2018 among 8‐9-year-old schoolchildren (N = 2554 and N = 2648, respectively). In 2018, spirometry and fractional exhaled nitric oxide (FeNO) measurements were also performed. Results: Current asthma (i.e., wheeze/asthma in the past 2 years) decreased from 6.9% in 2008 to 5.2% in 2013 and 4.3% in 2018 (p for trend < 0.001). The prevalence of lifetime (“ever had”) rhinoconjunctivitis also declined (5.1% in 2008, 4.4% in 2013, 3.0% in 2018; p for trend < 0.001), whereas that of lifetime eczema increased (10.8%, 13.6%, and 16.1%, respectively; p for trend < 0.001). The relative risk of current asthma in children with ever-had rhinoconjundtivitis was 7.73 in 2008, 6.00 in 2013, and 6.69 in 2018, whereas the relative risk in those with ever-had eczema was 5.15, 2.80, and 2.22, respectively. Among children with asthma, those with rhinoconjunctivitis had lower forced expiratory volume in the first second of expiration and higher FeNO values than those with eczema. Conclusion: The prevalence of asthma and rhinoconjunctivitis declined during the past decade in Greek schoolchildren, whereas the prevalence of eczema continued to rise. Nevertheless, the relationship between rhinoconjunctivitis and asthma remained strong, whereas the association between eczema and asthma appears to have weakened.