BFR strength training has become an increasingly popular, accessible and useful adjunct method to increase skeletal muscle strength and induce...]]>
There is consistent and compelling evidence linking raised type-2 biomarkers to exacerbation frequency
One of the challenges in the radiological interpretation of screening CT scans is the management of screen-detected pulmonary nodules. The prevalence of nodules in screening CT scans of the eligible population is high and ranges from 22% to 74%, depending on the...]]>
Published in 2016, the MITRA trial was arguably the most robust randomised controlled trial assessing the effect of SLIT (specifically HDM-SLIT) on the prevention of asthma attacks in mild-to-moderate allergic asthma.
Recent work by Kendall et al
A post-hoc analysis of the INCREASE trial and its open-label extension (OLE) was performed to evaluate whether inhaled treprostinil has a long-term survival benefit in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).
Two different models of survival were employed; the inverse probability of censoring weighting (IPCW) and the rank-preserving structural failure time (RPSFT) models both allow construction of a pseudo-placebo group, thereby allowing for long-term survival evaluation of patients with PH-ILD receiving inhaled treprostinil. Time-varying stabilised weights were calculated by fitting Cox proportional hazards models based on the baseline and time-varying prognostic factors to generate weighted Cox regression models with associated adjusted HRs.
In the INCREASE trial, there were 10 and 12 deaths in the inhaled treprostinil and placebo arms, respectively, during the 16-week randomised trial. During the OLE, all patients received inhaled treprostinil and there were 29 and 33 deaths in the prior inhaled treprostinil arm and prior placebo arm, respectively. With a conventional analysis, the HR for death was 0.71 (95% CI 0.46 to 1.10; p=0.1227). Both models demonstrated significant reductions in death associated with inhaled treprostinil treatment with HRs of 0.62 (95% CI 0.39 to 0.99; p=0.0483) and 0.26 (95% CI 0.07 to 0.98; p=0.0473) for the IPCW and RPSFT methods, respectively.
Two independent modelling techniques that have been employed in the oncology literature both suggest a long-term survival benefit associated with inhaled treprostinil treatment in patients with PH-ILD.
Low-dose CT screening can reduce lung cancer-related mortality. However, most screen-detected pulmonary abnormalities do not develop into cancer and it often remains challenging to identify malignant nodules, particularly among indeterminate nodules. We aimed to develop and assess prediction models based on radiological features to discriminate between benign and malignant pulmonary lesions detected on a baseline screen.
Using four international lung cancer screening studies, we extracted 2060 radiomic features for each of 16 797 nodules (513 malignant) among 6865 participants. After filtering out low-quality radiomic features, 642 radiomic and 9 epidemiological features remained for model development. We used cross-validation and grid search to assess three machine learning (ML) models (eXtreme Gradient Boosted Trees, random forest, least absolute shrinkage and selection operator (LASSO)) for their ability to accurately predict risk of malignancy for pulmonary nodules. We report model performance based on the area under the curve (AUC) and calibration metrics in the held-out test set.
The LASSO model yielded the best predictive performance in cross-validation and was fit in the full training set based on optimised hyperparameters. Our radiomics model had a test-set AUC of 0.93 (95% CI 0.90 to 0.96) and outperformed the established Pan-Canadian Early Detection of Lung Cancer model (AUC 0.87, 95% CI 0.85 to 0.89) for nodule assessment. Our model performed well among both solid (AUC 0.93, 95% CI 0.89 to 0.97) and subsolid nodules (AUC 0.91, 95% CI 0.85 to 0.95).
We developed highly accurate ML models based on radiomic and epidemiological features from four international lung cancer screening studies that may be suitable for assessing indeterminate screen-detected pulmonary nodules for risk of malignancy.
Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders.
We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis.
The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV.
Our study shows that height is an independent prognostic factor of resectable lung cancer.
Systematic screening is a potential tool for reducing the prevalence of tuberculosis (TB) and counteracting COVID-19-related disruptions in care. Repeated community-wide screening can also measure changes in the prevalence of TB over time.
We conducted serial, cross-sectional TB case finding campaigns in one community in Kampala, Uganda, in 2019 and 2021. Both campaigns sought sputum for TB testing (Xpert MTB/RIF Ultra) from all adolescents and adults. We estimated the prevalence of TB among screening participants in each campaign and compared characteristics of people with TB across campaigns. We simultaneously enrolled and characterised community residents who were diagnosed with TB through routine care and assessed trends in facility-based diagnosis.
We successfully screened 12 033 community residents (35% of the estimated adult/adolescent population) in 2019 and 11 595 (33%) in 2021. In 2019, 0.94% (95% CI: 0.77% to 1.13%) of participants tested Xpert positive (including trace). This proportion fell to 0.52% (95% CI: 0.40% to 0.67%) in 2021; the prevalence ratio was 0.55 (95% CI: 0.40 to 0.75)). There was no change in the age (median 26 vs 26), sex (56% vs 59% female) or prevalence of chronic cough (49% vs 54%) among those testing positive. By contrast, the rate of routine facility-based diagnosis remained steady in the 8 months before each campaign (210 (95% CI: 155 to 279) vs 240 (95% CI: 181 to 312) per 100 000 per year).
Following an intensive initial case finding campaign in an urban Ugandan community in 2019, the burden of prevalent TB as measured by systematic screening had decreased by 45% in 2021, despite the intervening COVID-19 pandemic.
Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT).
To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT.
MITRA (NCT01433523) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort.
An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p=0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p=0.006) for subjects with a higher number of elevated T2 biomarkers.
HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype.
The objective of this study is to compare the effectiveness of lower limb low-load blood flow restriction training (LL-BFRT) with high-load strength training (HL-ST) as part of an outpatient pulmonary rehabilitation programme on leg strength in patients with chronic obstructive pulmonary disease (COPD).
Participants were randomised to LL-BFRT or HL-ST (24 sessions). LL-BFRT was done at 30% 1-repetition maximum (1-RM) with 70% arterial occlusion pressure. HL-ST was done at 70% 1-RM. Primary outcome was isometric strength of knee extensors and flexors. Secondary outcomes were 1-RM, functional exercise capacity, physical activity, symptom burden and health-related quality of life. Perceptions of dyspnoea and leg fatigue were recorded after every exercise. We compared groups with t-tests.
We included 30 participants (13 women, 17 men, 64 (9) years, forced expiratory volume in 1 s 47 (18)% pred.), 24 completed the study. Isometric knee extensor strength improved to a clinically relevant degree in both legs in both groups (LL-BFRT: right leg 9 (20) Nm, left leg 10 (18) Nm; HL-ST: right leg 15 (26) Nm, left leg 16 (30) Nm, data are mean (SD)), without statistically significant or clinically relevant between-group differences (right leg mean difference= –6.4, 95% CI= –13.20 to 25.92 Nm, left leg mean difference= –5.6, 95% CI= –15.44 to 26.55 Nm). 1 min sit-to-stand test performance improved to a clinically relevant degree only in the LL-BFRT group (4 (4) vs 1 (5) repetitions). Interestingly, physical activity improved to a clinically relevant degree only in the LL-BFRT group (1506 (2441) vs –182 (1971) steps/day). LL-BFRT lowered perceived in-exercise dyspnoea and increased leg fatigue compared with HL-ST in the initial 12 trainings.
In patients with stable COPD undergoing outpatient pulmonary rehabilitation, LL-BFRT was not superior to HL-ST in improving leg strength. LL-BFRT led to similar strength gains as HL-ST while reducing perceptions of dyspnoea in the initial training phase.
It is unclear if type-2 inflammation is associated with accelerated lung function decline in individuals with asthma and chronic obstructive pulmonary disease (COPD). We tested the hypothesis that type-2 inflammation indicated by elevated blood eosinophils (BE) and fraction of exhaled nitric oxide (FeNO) is associated with accelerated lung function decline in the general population.
We included adults from the Copenhagen General Population Study with measurements of BE (N=15 605) and FeNO (N=2583) from a follow-up examination and assessed forced expiratory volume in 1 s (FEV1) decline in the preceding 10 years. Based on pre- and post-bronchodilator lung function, smoking history and asthma at follow-up examination, participants were assigned as not having airway disease, asthma with full reversibility (AR), asthma with persistent obstruction (APO), COPD, and not classifiable airflow limitation (NAL).
FEV1 decline in mL/year increased with 1.0 (95% CI 0.6 to 1.4, p<0.0001) per 100 cells/µL higher BE and with 3.2 (95% CI 2.0 to 4.5, p<0.0001) per 10 ppb higher FeNO. Adjusted FEV1 decline in mL/year was 18 (95% CI 17 to 20) in those with BE<300 cells/µL and FeNO<20 ppb, 22 (19–25) in BE≥300 cells/µL or FeNO≥20 ppb, and 27 (21–33) in those with BE≥300 cells/µL and FeNO≥20 ppb (p for trend<0.0001). Corresponding FEV1 declines were 24 (19–29), 33 (25–40) and 44 (31–56) in AR (0.002), 26 (14–37), 36 (12–60) and 56 (24–89) in APO (0.07), 32 (27–36), 31 (24–38) and 44 (24–65) in COPD (0.46), and 27 (21–33), 35 (26–45), and 37 (25–49) in NAL (0.10), respectively.
Type-2 inflammation indicated by elevated BE and FeNO is associated with accelerated FEV1 decline in individuals with chronic airway disease in the general population, and this association was most pronounced in an asthma-like phenotype.
Rare cystic lung diseases are increasingly recognised due the wider application of CT scanning making cystic lung disease management a growing part of respiratory care. Cystic lung diseases tend to have extrapulmonary features that can both be diagnostic but also require surveillance and treatment in their own right. As some of these diseases now have specific treatments, making a precise diagnosis is crucial. While Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia and lymphangioleiomyomatosis are becoming relatively well-known diseases to respiratory physicians, a targeted and thorough workup improves diagnostic accuracy and may suggest other ultrarare diseases such as light chain deposition disease, cystic pulmonary amyloidosis, low-grade metastatic neoplasms or infections. In many cases, diagnostic information is overlooked leaving uncertainty over the disease course and treatments.
This position statement from the Rare Disease Collaborative Network for cystic lung diseases will review how clinical, radiological and physiological features can be used to differentiate between these diseases.
We highlight that in many cases a multidisciplinary diagnosis can be made without the need for lung biopsy and discuss where tissue sampling is necessary when non-invasive methods leave diagnostic doubt. We suggest an initial workup focusing on points in the history which identify key disease features, underlying systemic and familial diseases and a clinical examination to search for connective tissue disease and features of genetic causes of lung cysts. All patients should have a CT of the thorax and abdomen to characterise the pattern and burden of lung cysts and extrapulmonary features and also spirometry, gas transfer and a 6 min walk test. Discussion with a rare cystic lung disease centre is suggested before a surgical biopsy is undertaken.
We suggest that this focused workup should be performed in all people with multiple lung cysts and would streamline referral pathways, help guide early treatment, management decisions, improve patient experience and reduce overall care costs. It could also potentially catalyse a national research database to describe these less well-understood and unidentified diseases, categorise disease phenotypes and outcomes, potentially leading to better prognostic data and generating a stronger platform to understand specific disease biology.
At review 4 months later, he reported ongoing breathlessness and cough productive of green sputum. Lung function tests showed a forced expiratory volume in 1 s (FEV1) of 2.4 L (67% predicted), forced vital capacity (FVC) of 4.2 L (97%), FEV1/FVC ratio of 0.56 and normal diffusing capacity of the lungs for carbon monoxide. Fractional exhaled nitric oxide was 34 ppb.
Eight weeks later, despite optimal inhaled therapy, his symptoms worsened, and he developed haemoptysis. CTPA showed progression of the right main bronchial wall thickening with mucous...]]>
Subsequent CT scan (
He subsequently developed chest pains—blood tests were unremarkable, with no pulmonary embolus (PE) on CT pulmonary angiogram (CTPA). A positron emission tomography-CT (PET-CT) scan showed low-to-moderate grade tracer uptake in the mass with low attenuation areas compatible with necrosis. There were no features of high-grade malignancy or metastatic disease. He described worsening swallowing and coughing...]]>
We present a case of a 20-year-old woman reporting polyarthritis, muscle weakness, dyspnoea and multiple intensive care unit admissions due to respiratory failure, without haemoptysis, since 4 months of age. The mother had systemic erythematous lupus. On physical examination, digital clubbing and mild desaturation were found. Laboratory tests demonstrated 1:640 nuclear homogeneous pattern antinuclear antibodies (ANA) and erythrocyte sedimentation rate (ESR) of 61 mm. Spirometry exhibited forced vital capacity of 53%.
High-resolution CT (HRCT) showed cysts and ground glass with reticular infiltrates (
What is the diagnosis of the patient?
This is a COPA syndrome case. The onset of respiratory and systemic symptoms in childhood, family history of autoimmunity, elevated ESR and...]]>
While surgery remains the primary curative-intent treatment for early-stage NSCLC, 30 to 55% of patients have tumour recurrence within 5 years. Neoadjuvant or adjuvant chemotherapy offers only 5% improvement in 5 year survival as compared with surgery alone. The AEGEAN trial (N Eng J Med 2023;389(18):1672–1684) was a phase 3, double-blind, placebo-controlled trail to investigate durvalumab. Patients with resectable stage II to IIIB NSCLC were randomly assigned to receive platinum-based chemotherapy plus durvalumab (400 patients) or placebo (402 patients) before surgery, followed by adjuvant durvalumab or placebo.
At the first interim analysis, significantly longer duration of event-free survival was observed with durvalumab than with placebo; the HR for disease progression, recurrence, or death was 0.68 (95% CI [95%confidence interval], 0.53 to 0.88; p=0.004). At 12 months, event-free survival was 73.4% in durvalumab group, compared with 64.5% with placebo. Furthermore, better rates of...]]>