Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients—High Efficacy of Rituximab

BackgroundSystemic sclerosis (SSc) patients often need immunosuppressive medication (IS) for disease control. If SSc is progressive despite IS, autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for selected SSc patients. aHSCT is effective with good available evidence, but not all patients achieve a treatment-free remission after aHSCT. Thus far, data about the need of IS after aHSCT in SSc is not published. The aim of this study was to investigate the use of IS after aHSCT, its efficacy, and the occurrence of severe adverse events (SAEs).MethodsTwenty-seven patients with SSc who had undergone aHSCT were included in this single-center retrospective cohort study. Clinical data, including IS, SAEs, and lung function data, were collected.ResultsSixteen of 27 (59.3%) patients received IS after aHSCT. Methotrexate, rituximab, mycophenolate, cyclophosphamide, and hydroxychloroquine were most commonly used. The main reason for starting IS was SSc progress. Nine patients received rituximab after aHSCT and showed an improvement in modified Rodnan skin score and a stabilization of lung function 2 years after rituximab. SAEs in patients with IS after aHSCT (50.0%) were not more common than in patients without IS (54.6%). SAEs were mostly due to SSc progress, secondary autoimmune diseases, or infections. Two deaths after aHSCT were transplantation related and three during long-term follow-up due to pulmonary arterial hypertension.ConclusionDisease progression and secondary autoimmune diseases may necessitate IS after aHSCT in SSc. Rituximab seems to be an efficacious treatment option in this setting. Long-term data on the safety of aHSCT is reassuring.

Epigenome-wide association study of lung function in Latino children and youth with asthma

Introduction DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population. Here, we aimed to identify DNA methylation patterns associated with lung function in pediatric asthma among Latinos. Results We conducted an EWAS in whole blood from 250 Puerto Rican and 148 Mexican American children and young adults with asthma. A total of five CpGs exceeded the genome-wide significance threshold of p = 1.17 × 10−7 in the combined analyses from Puerto Ricans and Mexican Americans: cg06035600 (MAP3K6, p = 6.13 × 10−8) showed significant association with pre-bronchodilator Tiffeneau–Pinelli index, the probes cg00914963 (TBC1D16, p = 1.04 × 10−7), cg16405908 (MRGPRE, p = 2.05 × 10−8), and cg07428101 (MUC2, p = 5.02 × 10−9) were associated with post-bronchodilator forced vital capacity (FVC), and cg20515679 (KCNJ6) with post-bronchodilator Tiffeneau–Pinelli index (p = 1.13 × 10−8). However, these markers did not show significant associations in publicly available data from Europeans (p > 0.05). A methylation quantitative trait loci analysis revealed that methylation levels at these CpG sites were regulated by genetic variation in Latinos and the Biobank-based Integrative Omics Studies (BIOS) consortium. Additionally, two differentially methylated regions in REXOC and AURKC were associated with pre-bronchodilator Tiffeneau–Pinelli index (adjusted p < 0.05) in Puerto Ricans and Mexican Americans. Moreover, we replicated some of the previous differentially methylated signals associated with lung function in non-Latino populations. Conclusions We replicated previous associations of epigenetic markers with lung function in whole blood and identified novel population-specific associations shared among Latino subgroups.

Relationship between gut microbiota and lung function decline in patients with chronic obstructive pulmonary disease: a 1-year follow-up study

Objective Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by a persistent limitation in airflow. Gut microbiota is closely correlated with lung inflammation. However, gut microbiota has not been studied in patients with declining lung function, due to chronic lung disease progression. Subjects and methods Stool samples were obtained from 55 patients with COPD that were in stable condition at enrolment (stage 1) and at a 1-year follow-up (stage 2). After extracting stool DNA, we performed next generation sequencing to analyse the distribution of gut microbiota. Results Patients were divided to control and declining lung function groups, based on whether the rate of forced expiratory volume in 1 s (FEV1) had declined over time. An alpha diversity analysis of initial and follow-up stool samples showed a significant difference in the community richness of microbiota in the declining function group, but not in the control group. At the phylum level, Bacteroidetes was more abundant in the control group and Firmicutes was more abundant in the declining function group. The Alloprevotella genus was more abundant in the control group than in the declining function group. At 1-year follow-up, the mean proportions of Acinetobacter and Stenotrophomonas significantly increased in the control and declining function groups, respectively. Conclusion Some community shifts in gut microbiota were associated with lung function decline in COPD patients under regular treatment. Future studies should investigate the mechanism underlying alterations in lung function, due to changes in gut bacterial communities, in COPD.

Long-term benefits of targeted micronutrition with the holoBLG lozenge in house dust mite allergic patients

Summary Purpose The long-term effects of targeted micronutrition with the holoBLG lozenge in house dust mite (HDM) allergic rhinoconjunctivitis (ARC) patients were evaluated at a follow-up visit in an allergen exposure chamber (AEC). Methods Patients who were supplemented for 3‑months with the holoBLG lozenge in a previous study with two controlled HDM-AEC challenges [visits: V1, V3] were recruited for a third AEC challenge (V5) 7–8 months after cessation of supplementation. Symptoms (nose, conjunctival, bronchial, others), well-being, and lung function parameters were recorded exactly as in the previous study. Primary endpoint was change in median Total Nasal Symptom Score (TNSS) at V5 compared to V1. Secondary endpoints included e.g. change in median Total Symptom Score (TSS) and the exploratory analysis of temporal evolution of symptom scores using linear mixed effects models. Results Of the 32 patients included in the original study, 27 could be recruited for the follow-up visit with a third AEC challenge. An improvement of 20% (p = 0.15) in the primary endpoint TNSS [V1: 2.5 (interquartile range [IQR]: 1–4), V5: 2.0 (IQR: 1–3)] was observed; 40% (p = 0.04) improvement was seen for the TSS [V1: 5.0 (IQR: 3–9), V5: 3.0 (IQR: 2–5.5)]. Analysis of temporal evolution of all symptom scores, and the personal well-being revealed sustained, clinically meaningful improvement at V5 compared to V1. No relevant lung function parameter differences were observed. Conclusions Sustained long-term reduction of TNSS (primary endpoint) and sustained long-term improvement of secondary endpoints (temporal evolution of all symptom scores and well-being) were demonstrated 7–8 months after cessation of holoBLG supplementation, indicative of a long-lasting nature of immune resilience induced by holoBLG. Trial registration The study was registered at clinicaltrials.gov (NCT04872868).

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.

Associations between sarcopenia with asthmatic prevalence, lung function and comorbidity

Background Sarcopenia was listed as a treatment trait in behavioral/risk factors of severe asthma, but studies between asthma and sarcopenia were scant. This study plans to determine the associations between sarcopenia with asthmatic prevalence, symptoms, lung function and comorbidity. Methods 15404 individuals from the China Health and Retirement Longitudinal Study(CHARLS) and 10263 individuals from Study on global AGEing and adult health(SAGE) in China were included in this study. Four components of this study were respectively used to assess bidirectional association in the prevalence between sarcopenia with asthma, and estimate the relationships between sarcopenia with asthmatic symptoms, lung function and comorbidity via generalized additive models. The 10-item Center for Epidemiological Studies–Depression Scale≥12 scores was classified as depression in CHARLS. Results In CHARLS and SAGE, the prevalence of sarcopenia in asthmatics was higher than those without asthma. Asthmatics with sarcopenia had a significantly increased prevalence of severe shortness of breath(sarcopenia yes vs no, adjusted OR=3.71, 95%CI: 1.43-9.60) and airway obstruction in SAGE(sarcopenia yes vs no, adjusted OR=6.82, 95%CI: 2.54-18.34) and an obvious reduction of PEF in CHARLS and SAGE(sarcopenia yes vs no, adjusted RR=0.86, 95%CI: 0.82-0.91) compared to asthmatics without sacropenia. The presence of sarcopenia was positively associated with the prevalence of chronic obstructive pulmonary disease(sarcopenia yes vs no, adjusted OR=5.76, 95%CI:2.01-16.5) and depression(sarcopenia yes vs no, adjusted OR=1.87, 95%CI:1.11-3.14) in asthmatics. Conclusions Our findings indicated that sarcopenia partakes in the development of asthma by affecting lung function and comorbidity and maybe considered a treatable trait of asthma management.

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