Respirology最新文献

Background and objective: Interstitial lung diseases (ILDs) are rare and severe respiratory conditions that may ultimately result in pulmonary fibrosis (PF). The objective of this study was to present the results of molecular diagnosis of early-onset ILD (from neonates to young adults < 50 years) in a reference genetic diagnostic laboratory.

Methods: DNAs from 699 index cases and 190 relatives were studied over 6 years by Sanger and/or targeted next generation sequencing of surfactant-related genes and other genes involved in early-onset ILD.

Results: Pathogenic/likely pathogenic variants were evidenced for 62 patients (8.9%). The genes most frequently involved were SFTPA2 (13/62), followed by ABCA3 (12/62) and SFTPC (10/62). Among index cases for whom precise clinical data were available (n = 542), indications associated with a high molecular diagnostic yield were pulmonary alveolar proteinosis (61.5%, 8/13; p < 0.0007); family history of ILD/PF and lung cancer (36.8%, 7/19; p = 0.0132) and newborns > 32 weeks gestation with neonatal respiratory distress (14.8%, 9/61). The proportion of positive molecular investigations culminated in two age groups over the lifespan: 23.3% (7/30) in children aged 1 to 10 years, and 18.3% (15/82) in adults aged 30 to 40 years. Over the 6-year period, 190 relatives were subjected to testing in order to perform segregation studies (n = 123) and/or predictive testing (n = 79).

Conclusion: This study highlights the specific patient's characteristics associated with a high or low molecular diagnostic yield in clinical practice. Furthermore, it emphasises the importance of establishing a molecular diagnosis in order to provide genetic counselling to the family.

Background and objective: Paediatric obstructive sleep apnea (OSA) has a distinct pathophysiology and management from that of adults, yet endotypic traits in this population remain underreported. Understanding how these traits vary by age and sex could provide insights into respiratory system development. This study aims to examine the association of age and sex with endotypic traits in children and adolescents with OSA.

Methods: Between April 2020 and September 2024, we prospectively enrolled 88 patients aged ≤ 18 years who were referred to a single clinical sleep center in Taiwan for in-laboratory diagnostic polysomnography. Patients with an apnea-hypopnea index (AHI) ≥ 1 h^-1 were included. Endotypic traits were estimated using polysomnographic signals. Linear regression analysis was performed to assess the associations of endotypic traits with AHI, age, and sex.

Results: Poor compensation, worse collapsibility, and high loop gain were associated with higher AHI, with compensation explaining the largest variance (12.85%) among all endotypic traits. Patients older than 12 years exhibited a more compromised upper airway (V _min: 64.3 vs. 71.4% eupnea) and higher loop gain (LG₁: 0.45 vs. 0.34) than younger patients, independent of AHI. No significant sex differences in endotypic traits were observed.

Conclusions: In addition to upper airway collapsibility, inadequate compensatory activity of the dilator muscles significantly contributed to higher AHI in paediatric patients with OSA. The age-related decrease in upper airway patency may result from the interplay between upper airway and craniofacial development.

Background and objectives: Inhaled corticosteroids have been proposed as treatment for acute COVID-19 infection in the community. We sought to determine the efficacy and safety of inhaled ciclesonide 320 mcg daily for 14 days compared to placebo in reducing the time to first recovery from all symptoms within 28 days of randomisation.

Methods: We conducted a two-arm, double blind, placebo-controlled, community-based randomised trial. Participants received inhaled ciclesonide 320 mcg daily or matching placebo for 14 days. The primary outcome was time to recovery of symptoms to day 28. An updated systematic review of all controlled trials of inhaled corticosteroids for acute COVID-19 was then undertaken.

Results: There were 189 people randomised and 185 completed treatment; 96% were COVID-19 vaccinated. No difference was seen in the time to first recovery using a proportional hazards analysis, recovery rate ratio 1.04 (95% CI; 0.77, 1.40). The median time to recovery with ciclesonide was 7 days (95% CI 6-9), compared with placebo of 7 days (95% CI 6-9), p = 0.84. There were no significant differences in secondary outcomes, including time to sustained recovery and respiratory symptoms. The treatment was safe and well tolerated.

Conclusion: In a highly vaccinated (> 90%) population exposed to Omicron variants of SARS-CoV-2, the addition of inhaled ciclesonide had no effect on accelerating recovery from acute symptoms. These trial results and updated combined evidence of placebo-controlled trials do not support the use of inhaled corticosteroids for the treatment of COVID-19.

Trial registration: ACTRN12620000566932.

Background and objective: Our previous study demonstrated that a summed score derived from six cardiopulmonary exercise testing (CPET) parameters could predict 1-year mortality in patients with interstitial lung disease (ILD). However, its long-term prognostic value across different ILD aetiologies remains unclear. This study aimed to assess the predictive performance of CPET-derived parameters for long-term outcomes in patients with idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated ILD (CTD-ILD).

Methods: In this prospective cohort study, 210 patients newly diagnosed with ILD between 2018 and 2022 at a tertiary medical centre underwent CPET. A CPET-derived summed score was evaluated for its association with a composite outcome of all-cause mortality or lung transplantation. Cox regression and receiver operating characteristic curve analyses were used to examine predictive ability and identify the optimal cutoff value. Kaplan-Meier survival analysis and log-rank tests compared event-free survival in IPF and CTD-ILD patients.

Results: A summed score incorporating five CPET-derived variables was an independent predictor of the composite outcome. Patients with scores of 2-5 had markedly lower event-free survival (44.2%) than those with scores of 0-1 (88.3%). The score demonstrated consistent predictive value in both IPF and CTD-ILD.

Conclusion: The CPET-derived summed score is a useful prognostic tool for predicting all-cause mortality or the need for lung transplantation in newly diagnosed ILD patients. It also retains predictive accuracy for long-term outcomes in both IPF and CTD-ILD. External validation in other ILD subtypes is warranted.

Trial registration: ClinicalTrials.gov identifier: NCT06476470.

Background and objectives: Small lung nodules can be difficult to identify via thoracoscopy, thereby making thoracoscopic sublobar resection challenging. We have developed a protocol of preoperative lung nodule marking using robotic-assisted bronchoscopy (RAB), followed by thoracoscopic sublobar resection in one setting. We evaluated the outcomes of patients undergoing Robotic One Anaesthetic Marking And Resection (ROMAR).

Methods: We reviewed the records of all patients undergoing ROMAR between January 2023 and March 2025. The primary outcome was the success of marking, defined as dye visualisation on the pleural surface during thoracoscopy and the resected specimen containing the lesion.

Results: A total of 119 lesions in 111 patients were included. The mean lesion size was 14.2 mm (SD ± 5.9 mm). The majority of the lesions (77.3%) were non-solid. An average of 1.0 cc of dye was injected per target. RATS and VATS were performed in 77 and 31 patients, respectively. The initial resection procedures were wedge resection in 94 patients (84.7%), segmentectomy in 16 patients (14.4%), and lobectomy in 1 patient (due to adhesions). In 6 cases, dye was not visible on the pleural surface during thoracoscopy. In 5 patients (4.5%), no tumour was identified on the initial frozen section. Therefore, initial sublobar resection was successful in 99 patients (89.2%). No significant complications were noted.

Conclusions: ROMAR facilitated successful thoracoscopic sublobar resection of small lung nodules in approximately 90% of the cases. It is safe and can be easily adopted at most centres performing robotic bronchoscopy and thoracoscopic lung surgery.

Background and objective: Relatively little is known about how to maximise participation in lung cancer screening for Australians at high risk of developing the disease. A discrete choice experiment was conducted to elicit and quantify preferences of Australians eligible for lung cancer screening (LCS) to maximise participation in the National Lung Cancer Screening Program (NLCSP) and estimate likely participation.

Methods: Respondents completed an online survey of six LCS factors or 'attributes' (invitation to screen, eligibility assessment, appointment booking, model of care, health care worker support and out-of-pocket costs). Results were analysed using mixed logit (MIXL), multinomial logit (MNL) and latent class analysis to explore heterogeneity in respondents' choices. Willingness to pay (WTP) for screening attributes were estimated based on the ratio of the coefficient on attributes to cost.

Results: Respondents (n = 757) were aged 50-70 years with smoking histories (> 30 pack-year history and either currently smoke or quit ≤ 10 years). The MIXL showed that participants preferred support from a program navigator, with the highest estimated WTP of $24, plus personalised invitations and lower screening costs. The results identified participation rates that could be achieved through optimal LCS program design, across the most optimistic screening program scenario (87.4%), the scenario proposed in the NLCSP (51.5%) and the least preferred scenario (35.0%).

Conclusion: The results are highly relevant for the NLCSP, which commenced on 1 July 2025. Potential participants place significant value on program navigators, a role not funded within the program, which could significantly improve uptake.

Background and objective: The role of lung ultrasound's (LUS) in diagnosing and assessing connective tissue disease (CTD)-related interstitial lung disease (ILD) remains controversial. We aimed to evaluate the diagnostic performance of a quantitative LUS score and the correlations between LUS scores and quantitative computed tomography (QCT) parameters in patients with CTD-ILD.

Methods: This prospective study included individuals with CTD and clinical suspicion of ILD attending our hospital between December 2023 and November 2024. LUS was performed using a 14 intercostal scanning protocol; high-resolution computed tomography (HRCT) was analysed using artificial intelligence-based QCT software. Participants underwent pulmonary function tests (PFTs) and completed the King's Brief Interstitial Lung Disease (KBILD) questionnaire. We analysed the LUS score's diagnostic efficacy and its correlations with QCT findings, PFT results, and KBILD scores.

Results: Among 206 patients with CTD enrolled, 145, 30, and 31 were categorised into ILD, preclinical ILD, and non-ILD groups, respectively. Patients with ILD exhibited higher LUS scores and QCT parameters but lower PFT results and KBILD scores than those without ILD or with preclinical ILD. At cutoff scores of 5.5 and 14.5, LUS distinguished non-ILD from preclinical ILD and ILD with sensitivities of 93.1% and 93.8% (specificities: 83.9% and 86.9%, respectively). LUS scores correlated positively with all QCT parameters, particularly fibrosis extent (r = 0.784; p < 0.001). Median LUS scores differed significantly among PFT and HRCT-defined ILD extent groups.

Conclusion: LUS facilitates early diagnosis of CTD-ILD, and quantitative LUS score correlates with QCT-defined ILD extent.

Trial registration: Chinese Clinical Trial Registry (registration number ChiCTR2400080909).

Background and objective: Checkpoint inhibitor pneumonitis (CIP) is a serious immune-related adverse event. Patients with interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD) may be at increased risk, but data comparing these populations is limited. We aimed to evaluate differences in CIP incidence, onset, recurrence, and outcomes among patients with ILD, COPD, and those without pre-existing lung disease.

Methods: We conducted a retrospective cohort study using the TriNetX Research Network, identifying patients who received immune checkpoint inhibitors (ICIs) between January 2017 and January 2023. Patients were stratified into ILD, COPD, and control groups. CIP was identified using ICD codes. Propensity score matching (1:1:1) was used to adjust for baseline characteristics. Outcomes included CIP incidence, time to onset, recurrence, hospitalisation, and mortality.

Results: Among 184,000+ ICI recipients, 3147 had ILD, 8657 had COPD, and 47,031 had no known lung disease. After matching (n = 3147/group), CIP incidence was highest in ILD patients (4.6%) compared to COPD (1.9%) and controls (1.5%) (p < 0.001). Time to CIP onset was similar across groups. ILD patients with CIP had higher recurrence (16.4% vs. 9.1% and 8.3%) and higher all-cause hospitalisation (61% vs. 40% and 39%) compared to COPD and control groups. All-cause mortality was also higher in the ILD-CIP group (41.1%).

Conclusion: ILD significantly increases the risk of developing CIP and worsens associated outcomes, including recurrence and mortality. These findings support closer surveillance and risk stratification in ICI-treated patients with underlying ILD.