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The latest medical research on Respiratory Medicine

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Combining small airway parameters with conventional parameters obtained during spirometry to diagnose airflow obstruction: A cross-sectional study.

Respirology

The use of small airway parameters generated by spirometry, namely forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF25%-75%) and forced expiratory flow at 50% and 75% of FVC (FEF50% and FEF75%, respectively), is widely discussed. We evaluated the importance of these spirometric parameters in a large Chinese population.

We conducted a cross-sectional observational study in which spirometry and bronchodilator responsiveness (BDR) data were collected in a healthcare centre from May 2021 to August 2022 and in a tertiary hospital from January 2017 to March 2022. Discordance was assessed between the classification of test results by the large airway parameters of forced expiratory volume in 1 second (FEV1) and FEV1/FVC ratio and by the small airway parameters of FEF25%-75%, FEF75% and FEF50%. The predictive power of Z-scores of spirometric parameters for airflow limitation and BDR was assessed using receiver operating characteristic curves.

Our study included 26,658 people. Among people with a normal FVC (n = 14,688), 3.7%, 4.5% and 3.6% of cases exhibited normal FEV1/FVC ratio but impaired FEF25%-75%, FEF75% and FEF50%, respectively, while 6.8%-7.0% of people exhibited normal FEV1 but impaired FEF25%-75%, FEF75% and FEF50%. Using the Z-scores of combining both large and small airway parameters in spirometry showed the best area under the curve for predicting airflow limitation (0.90; 95% CI 0.87-0.94) and predicting BDR (0.72; 95% CI 0.71-0.73).

It is important to consider both large and small airway parameters in spirometry to avoid missing a diagnosis of airflow obstruction.

Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

Respirology

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease.

We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available.

Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS.

Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

Aberrant Long-Chain Fatty Acid Metabolism Associated with Evolving Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

Am J Physiol

We sought to investigate differential metabolism in patients with systemic sclerosis (SSc) who develop pulmonary arterial hypertension (PAH) versus...

A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.

Am J Physiol

Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal mo...

Progesterone amplifies allergic inflammation and airway pathology in association with higher lung ILC2 responses.

Am J Physiol

Perimenstrual worsening of asthma occurs in up to 40% of asthmatic women, leading to increased acute exacerbations requiring clinical care. The rol...

Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

Am J Physiol

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasor...

A Novel DNase Assay Reveals Low DNase Activity in Severe Asthma.

Am J Physiol

Secreted deoxyribonucleases (DNases), such as DNase-1 and DNase-IL3, degrade extracellular DNA, and endogenous DNases have roles in resolving airwa...

Advances in lung transplantation: 60 years on.

Respirology

Lung transplantation is a well-established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all ...

Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study.

Thorax

A usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA)-associated interstitial lung disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors.

We used two-sample bidirectional Mendelian randomisation (MR) to test the hypothesis of a causal effect of RA on UIP and of UIP on RA, using variants from genome-wide association studies (GWAS) of RA (separately for seropositive (18 019 cases and 991 604 controls) and seronegative (8515 cases and 1 015 471 controls) RA) and of IPF (4125 cases and 20 464 controls) as genetic instruments. Sensitivity analyses were conducted to assess the robustness of the results to violations of the MR assumptions.

IPF showed a significant causal effect on seropositive RA, with developing IPF increasing the risk of seropositive RA (OR=1.06, 95% CI: 1.04 to 1.08, p<0.001) which was robust under all models. For the MR in the other direction, seropositive RA showed a significant protective effect on IPF (OR=0.93; 95% CI: 0.87 to 0.99; p=0.032), but the effect was not significant when sensitivity analyses were applied. This was likely because of bias due to exclusion of patients with RA from among the cases in the IPF GWAS, or possibly because our genetic instruments did not fully capture the effect of the complex human leucocyte antigen region, the strongest RA genetic risk factor.

Our findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between UIP and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The significant causal effect of IPF on seropositive RA suggests that pathomechanisms involved in the development of UIP may promote RA, and this may help inform future guidelines on screening for ILD in patients with RA.

Inhibition of GBP5 activates autophagy to alleviate inflammatory response in LPS-induced lung injury in mice.

Exp Lung Res

Pulmonary emphysema is a condition that causes damage to the lung tissue over time. GBP5, as part of the guanylate-binding protein family, is dysregulated in mouse pulmonary emphysema. However, the role of GBP5 in lung inflammation in ARDS remains unveiled.

To investigate whether GBP5 regulates lung inflammation and autophagy regulation, the study employed a mouse ARDS model and MLE-12 cell culture. Vector transfection was performed for the genetic manipulation of GBP5. Then, RT-qPCR, WB and IHC staining were conducted to assess its transcriptional and expression levels. Histological features of the lung tissue were observed through HE staining. Moreover, ELISA was conducted to evaluate the secretion of inflammatory cytokines, autophagy was assessed by immunofluorescent staining, and MPO activity was determined using a commercial kit.

Our study revealed that GBP5 expression was altered in mouse ARDS and LPS-induced MLE-12 cell models. Moreover, the suppression of GBP5 reduced lung inflammation induced by LPS in mice. Conversely, overexpression of GBP5 diminished the inhibitory impact of LPS on ARDS during autophagy, leading to increased inflammation. In the cell line of MLE-12, GBP5 exacerbates LPS-induced inflammation by blocking autophagy.

The study suggests that GBP5 facilitates lung inflammation and autophagy regulation. Thus, GBP5 could be a potential therapeutic approach for improving ARDS treatment outcomes, but further research is required to validate these findings.

Therapeutic bronchoscopy for malignant central airway obstructions caused by non-bronchogenic cancers: Results from the EpiGETIF registry.

Respirology

Little is known about malignant central airway obstruction (MCAO) complicating the metastatic spread of non-bronchogenic solid cancers (NBC) and their bronchoscopic management. This study aimed to describe the epidemiology of this population and determine prognostic factors before therapeutic bronchoscopy (TB).

In this multicenter study using the EpiGETIF registry, we analysed patients treated with TB for MCAO caused by NBC between January 2019 and December 2022.

From a database of 2389 patients, 436 patients (18%) with MCAO and NBC were identified. After excluding patients with direct local invasion, 214 patients (8.9%) were analysed. The main primaries involved were kidney (17.8%), colon (16.4%), sarcoma (15.4%), thyroid (8.9%) and head and neck (7.9%) cancers. Most patients (63.8%) had already received one or more lines of systemic treatment. Obstructions were purely intrinsic in 58.2%, extrinsic in 11.1% and mixed in 30.8%. Mechanical debulking was used in 73.4% of cases, combined with thermal techniques in 25.6% of cases. Airway stenting was required in 38.4% of patients. Median survival after TB was 11.2 months, influenced by histology (p = 0.002), performance status (p = 0.019), initial hypoxia (HR 1.45 [1.01-2.18]), prior oncologic treatment received (HR 1.82 [1.28-2.56], p < 0.001) and assessment of success at the end of the procedure (HR 0.66 [0.44-0.99], p < 0.001). Complications rate was 8.8%, mostly mild, with no procedure-related mortality.

TB for MCAO caused by a NBC metastasis provides rapid improvement of symptoms and prolonged survival. Patients should be promptly referred by medical oncologists for bronchoscopic management based on the prognostic factors identified.

Diagnostic Approach to Interstitial Lung Diseases Associated with Connective Tissue Diseases.

Seminars in Respiratory and Critical

Interstitial lung disorders are a group of respiratory diseases characterized by interstitial compartment infiltration, varying degrees of infiltra...