Respirology最新文献

Background and objective: Understanding the seasonal behaviours of respiratory viruses is crucial for preventing infections. We evaluated the seasonality of respiratory viruses using time-series analyses.

Methods: This study analysed prospectively collected nationwide surveillance data on eight respiratory viruses, gathered from the Korean Influenza and Respiratory Surveillance System. The data were collected on a weekly basis by 52 nationwide primary healthcare institutions between 2015 and 2019. We performed Spearman correlation analyses, similarity analyses via dynamic time warping (DTW) and seasonality analyses using seasonal autoregressive integrated moving average (SARIMA).

Results: The prevalence of rhinovirus (RV, 23.6%-31.4%), adenovirus (AdV, 9.2%-16.6%), human coronavirus (HCoV, 3.0%-6.6%), respiratory syncytial virus (RSV, 11.7%-20.1%), influenza virus (IFV, 11.7%-21.5%), parainfluenza virus (PIV, 9.2%-12.6%), human metapneumovirus (HMPV, 5.6%-6.9%) and human bocavirus (HBoV, 5.0%-6.4%) were derived. Most of them exhibited a high positive correlation in Spearman analyses. In DTW analyses, all virus data from 2015 to 2019, except AdV, exhibited good alignments. In SARIMA, AdV and RV did not show seasonality. Other viruses showed 12-month seasonality. We describe the viruses as winter viruses (HCoV, RSV and IFV), spring/summer viruses (PIV, HBoV), a spring virus (HMPV) and all-year viruses with peak incidences during school periods (RV and AdV).

Conclusion: This is the first study to comprehensively analyse the seasonal behaviours of the eight most common respiratory viruses using nationwide, prospectively collected, sentinel surveillance data.

Background and objective: Uncontrolled asthma in patients treated for mild/moderate disease could be caused by non-pulmonary treatable traits (TTs) that affect asthma control negatively. We aimed to identify demographic characteristics, behavioural (smoking) and extrapulmonary (obesity, comorbidities) TTs and the risk for future exacerbations among patients with uncontrolled asthma prescribed step 1-3 treatment according to the Global Initiative for Asthma (GINA).

Methods: Twenty-eight thousand five hundred eighty-four asthma patients (≥18 y) with a registration in the Swedish National Airway Register between 2017 and 2019 were included (index-date). The database was linked to other national registers to obtain information on prescribed drugs 2-years pre-index and exacerbations 1-year post-index. Asthma treatment was classified into step 1-3 or 4-5, and uncontrolled asthma was defined based on symptom control, exacerbations and lung function.

Results: GINA step 1-3 included 17,318 patients, of which 9586 (55%) were uncontrolled (UCA 1-3). In adjusted analyses, UCA 1-3 was associated with female sex (OR 1.34, 95% CI 1.27-1.41), older age (1.00, 1.00-1.00), primary education (1.30, 1.20-1.40) and secondary education (1.19, 1.12-1.26), and TTs such as smoking (1.25, 1.15-1.36), obesity (1.23, 1.15-1.32), cardiovascular disease (1.12, 1.06-1.20) and depression/anxiety (1.13, 1.06-1.21). Furthermore, UCA 1-3 was associated with future exacerbations; oral corticosteroids (1.90, 1.74-2.09) and asthma hospitalization (2.55, 2.17-3.00), respectively, also when adjusted for treatment step 4-5.

Conclusion: Over 50% of patients treated for mild/moderate asthma had an uncontrolled disease. Assessing and managing of TTs such as smoking, obesity and comorbidities should be conducted in a holistic manner, as these patients have an increased risk for future exacerbations.

Background and objective: As the presentation of pulmonary nodules increases, the importance of a safe and accurate method of sampling peripheral pulmonary nodules is highlighted. First-generation robotic bronchoscopy has successfully assisted navigation and improved peripheral reach during bronchoscopy. Integrating tool-in-lesion tomosynthesis (TiLT) may further improve yield.

Methods: We performed a first-in-human clinical trial of a new robotic electromagnetic navigation bronchoscopy system with integrated digital tomosynthesis technology (Galaxy System, Noah Medical). Patients with moderate-risk peripheral pulmonary nodules were enrolled in the study. Robotic bronchoscopy was performed using electromagnetic navigation with TiLT-assisted lesion guidance. Non-specific results were followed up until either a clear diagnosis was achieved or repeat radiology at 6 months demonstrated stability.

Results: Eighteen patients (19 nodules) were enrolled. The average lesion size was 20 mm, and the average distance from the pleura was 11.6 mm. The target was successfully reached in 100% of nodules, and the biopsy tool was visualized inside the target lesion in all cases. A confirmed specific diagnosis was achieved in 17 nodules, 13 of which were malignant. In one patient, radiological monitoring confirmed a true non-malignant result. This translates to a yield of 89.5% (strict) to 94.7% (intermediate). Complications included one pneumothorax requiring observation only and another requiring an overnight chest drain. There was one case of severe pneumonia following the procedure.

Conclusion: In this first-in-human study, second-generation robotic bronchoscopy using electromagnetic navigation combined with integrated digital tomosynthesis was feasible with an acceptable safety profile and demonstrated a high diagnostic yield for small peripheral lung nodules.

Background and objective: A disintegrin and metalloprotease 33 (ADAM33) is associated with asthma susceptibility, and its genetic variations impact susceptibility and disease severity. However, the mechanisms remain unclear. This study aimed to investigate ADAM33 single nucleotide polymorphisms (SNPs) in childhood asthma susceptibility and explore their regulatory mechanisms.

Methods: Eleven selected SNPs in ADAM33 were genotyped and identified the association with asthma susceptibility. In the validation cohort, we measured plasma sADAM33 levels and compared them with disease severity among children with different SNP genotypes. Computational predictions identified miRNAs targeting the SNP, and the impact of the SNP on miRNA regulation was confirmed using a dual luciferase reporter system. Finally, we validated the regulatory role of miRNAs on ADAM33 expression using an in vitro model with upregulated ADAM33 expression.

Results: Only rs3918400 was associated with asthma susceptibility. In the validation cohort, children with allergic asthma exhibited higher plasma sADAM33 levels. Among asthmatic children, those with the rs3918400 CT/TT genotype had higher sADAM33 levels, poorer asthma control, more severe airway hyper-responsiveness, lower FEV₁% and higher dust mite-specific IgE activity compared to those with the CC genotype. miR-3928-5p bound strongly to the rs3918400 C allele and effectively reduced ADAM33 protein expression in CC genotype cells. However, the binding affinity of miR-3928-5p to the T allele was weaker, resulting in diminished negative regulation of protein expression.

Conclusion: The rs3918400 SNP affects the negative regulation of ADAM33 by miR-3928-5p, potentially participating in a complex interplay of processes related to childhood asthma susceptibility.

Background and objective: Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV₁, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort.

Methods: Analysing data of 1364 patients from the German observational COSYCONET-cohort, disease progression and improvement patterns were assessed for their impact on mortality via Cox hazard regression models. Association of biomarkers and COPD Assessment test items with phenotypes of disease progression or improvement were evaluated using logistic regression and random forest models.

Results: Increased risk of 18-54-month mortality was linked to decrease in KCO % predicted (7.5% increments) and FEV₁ (20 mL increments), increase in RV/TLC (2% increments) and SGRQ (≥6 points), and an exacerbation grade of 2 at 18 months. Decrease in KCO % predicted ≥7.5% and an increase of RV/TLC ≥2% were the most frequent measures of 18-month disease progression occurring in ~52% and ~46% of patients, respectively. IL-6 and CRP thresholds exhibited significant associations with medium- and long-term disease measures.

Conclusion: In a multicentric cohort of COPD, new markers of current disease activity predicted mid-term mortality and could not be anticipated by baseline biomarkers.