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Purpose of the research: transbronchial lung cryobiopsy has been recently accepted as a valid and less invasive alternative to surgical lung biopsy. The purpose of this randomized controlled study was to evaluate, for the first time, the quality and safety of biopsy specimens obtained by using the new disposable 1.7-mm cryoprobe compared with the standard re-usable 1.9 mm cryoprobe in the diagnosis of diffuse parenchymal lung diseases. Methods: 60 consecutive patients were prospectively enrolled and randomly assigned to two different groups: 1.9 mm (group A) and 1.7 mm (group B); primary endpoints were pathological and multidisciplinary diagnostic yield, sample size and complication rate. Principal results: the pathological diagnostic yield of cryobiopsy was 100% in group A and 93.3% in group B (p = 0.718); cryobiopsy median diameter was 6.8 mm in group A and 6.7 mm in group B (p = 0,5241). Pneumothorax occurred in 9 patients in group A and 10 in group B (p = 0.951); mild-to-moderate bleeding in 7 cases and 9 cases in group A and B respectively (p = 0.559). No death or severe adverse events were observed. Conclusions: there was no statistically significant difference between the two groups, regarding diagnostic yield, adverse events and sampling adequacy.

Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection, hospitalisation and death in adults.

Methods: Based on evidence regarding the impact of RSV on adult populations at risk for severe infection and the efficacy and safety of RSV vaccines, the Portuguese Society of Pulmonology, the Portuguese Association of General and Family Medicine, the Portuguese Society of Cardiology, the Portuguese Society of Infectious Diseases and Clinical Microbiology, the Portuguese Society of Endocrinology, Diabetes and Metabolism, and the Portuguese Society of Internal Medicine endorses this position paper with recommendations to prevent RSV-associated disease and its complications in adults through vaccination.

Conclusion: The RSV vaccine is recommended for people aged ≥50 years with risk factors (chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, diabetes, chronic kidney disease, chronic liver disease, immunocompromise, frailty, dementia, and residence in a nursing home) and all persons aged ≥60 years. If it cannot be made available to this population, then the vaccine should be prioritised for individuals aged ≥75 years and those aged ≥50 years with risk factors. The vaccine should preferably be given between September and November and can be co-administered with the influenza vaccine. Ongoing studies on RSV vaccines may justify extending these recommendations in the future.

New ultrathin bronchoscopes (UTBs) enable the inspection and biopsy of small airways, potentially offering diagnostic advantages in sarcoidosis. In this prospective study, patients with suspected sarcoidosis underwent airway inspection with a UTB. Observed airway abnormalities were categorised into six predefined patterns. UTB-directed small airway biopsies (SABs) were collected from the upper lobes following a standardised procedure. We evaluated the prevalence and patterns of SAAs, as well as the diagnostic yield of UTB-directed SAB. Among 79 participants, 65 (82.3%) were diagnosed with sarcoidosis. Small airway abnormalities were identified in 26/65 (40%) patients, predominantly in those with parenchymal involvement on CT compared to those with lymphadenopathy only (58.1% VS. 23.5%, P = 0.005). The diagnostic yield of SABs for detecting granulomas was significantly higher in patients with SAAs than in those without (65.4% VS. 23.1%, P = 0.001) and in patients with parenchymal disease on CT compared to those without (54.8% VS. 26.5%, P = 0.02). Notably, random biopsies taken under direct visualisation from small airway carinas revealed peribronchiolar parenchyma in 23% of the patients. Small airway abnormalities are prevalent in sarcoidosis patients with parenchymal involvement, and biopsying these abnormalities yields a high rate of granuloma detection.

Importance: Prior study in healthy subjects has shown a reduction of partial pressure of arterial oxygen (PaO₂) by -1.60 kPa/kilometre of altitude gain. However, the association of altitude-related change in PaO₂ and altitude-related adverse health effects (ARAHE) in patients with chronic obstructive pulmonary disease (COPD) remain unknown.

Objective: To provide an effect size estimate for the decline in PaO₂ with each kilometre of altitude gain and to identify ARAHE in relation to altitude in patients with COPD. www.crd.york.ac.uk/prospero: CRD42020217938.

Data sources: A systematic search of PubMed and Embase was performed from inception to May 30, 2023.

Study selection: Peer-reviewed and prospective studies in patients with COPD staying at altitudes >1500 m providing arterial blood gases within the first 3 days at the target altitude.

Data extraction and synthesis: Aggregate data (AD) on study characteristics were extracted, and individual patient data (IPD) were requested. Estimates were pooled using random-effects meta-analysis.

Main outcome and measures: Relative risk estimates and 95 % confidence intervals for the association between PaO₂ and altitude in patients with COPD.

Results: Thirteen studies were included in the AD analysis, of which 6 studies (222 patients, 45.2 % female) provided IPD, thus were included in the quantitative analysis. The estimated effect size of PaO₂ was -0.84 kPa [95 %CI, -0.92 to -0.76] per 1000 m of altitude gain (I²=65.0 %, P < 0.001). In multivariable regression analysis, COPD severity, baseline PaO₂, age and time spent at altitude were predictors for PaO₂ at altitude. Overall, 37.8 % of COPD patients experienced an ARAHE, whereas older age, female sex, COPD severity, baseline PaO_2, and target altitude were predictors for the occurrence of ARAHE (area under ROC curve: 0.9275, P < 0.001).

Conclusions and relevance: This meta-analysis, providing altitude-related decrease in PaO₂ and risk of ARAHE in patients with COPD ascending to altitudes >1500 m, revealed a lower altitude-related decrease in PaO₂ in COPD patients compared with healthy. However, these findings might improve patient care and facilitate decisions about initiating preventive measures against hypoxaemia and ARAHE in patients with COPD planning an altitude sojourn or intercontinental flight, i.e. supplemental oxygen or acetazolamide.

Background: Non-invasive helmet respiratory support is suitable for several clinical conditions. Continuous-flow helmet CPAP systems equipped with HEPA filters have become popular during the recent Coronavirus pandemic. However, HEPA filters generate an overpressure above the set PEEP.

Methods: A lung simulator was used to mimic patient respiratory mechanics and effort. Compared to room air spontaneous breathing, the additional inspiratory effort attributable to helmet CPAP (ΔPmusHelmet) was recorded at different continuous-flow rates (30-150 L/min), PEEP levels (5, 10, 12.5 cmH2O) and respiratory rates (15, 20, 25, 30 breaths/minute), both with and without a HEPA filter at the outlet port.

Results: Helmet pressure swings during inspiration largely explained ΔPmusHelmet variations (p<0.001, Spearman's Rho=0.964). The lowest ΔPmusHelmet levels (0.2 [0; 0.4] cmH2O) were frequently recorded (>70%) at a 90 L/min flow rate. Higher ΔPmusHelmet levels were recorded when the continuous-flow was lower than the peak inspiratory flow (3.7 [3.1; 5.6] cmH2O, p<0.001) or when a HEPA filter was used (2.7 [2.2; 3.5], p<0.001). Increasing the flow rate resulted in higher overpressure levels, particularly with a HEPA filter (p<0.001). Overpressure levels correlated with ΔPmusHelmet (p<0.001, Spearman's Rho=0.598).

Conclusions: Helmet pressure swings below PEEP lead to additional inspiratory efforts. The HEPA filter acts as a flow resistor, generating an overpressure leading to increased respiratory effort. The continuous-flow rate should be titrated high enough to slightly exceed the peak inspiratory flow; however, further flow increase is not recommended as it leads to an increase in overpressure and helmet pressure swings below PEEP.

Health systems in low- and middle-income countries face the challenge of addressing the growing burden of non-communicable diseases (NCDs) with scarce resources to do so. There are cost-effective interventions that can improve management of the most common NCDs, but many remain poorly implemented. One example is fixed dose combinations (FDCs) of medications for hypertension. Included in WHO's Essential Medicines List, FDCs combine two or more blood pressure lowering agents into one pill and can reduce burden on patients and the health system. However, implementation of FDCs globally is poor. We aimed to identify health systems factors affecting implementation of evidence-based interventions for NCDs, and opportunities to address these, using the case study of FDCs in Kenya. We conducted semi-structured interviews with 39 policy-makers and healthcare workers involved in hypertension treatment policy and identified through snowball sampling. Interview data were analyzed thematically, using the Access Framework to categorize themes. Our interviews identified factors operating at the global, national, county, and provider levels. These include lack of global implementation guidance, context specific cost-effectiveness data, or prioritization by procurement agencies and clinical guidelines; perceived high cost; poor data for demand forecasting; insufficient budget for procurement of NCD medications; absence of prescriber training and awareness of clinical guidelines; and habitual prescribing behavior and understaffing limiting capacity for change. We propose specific strategies to address these. The findings of this work can inform efforts to improve implementation of other evidence-based interventions for NCDs in low-income settings.

Introduction: Previous studies of anti-IL-5/IL-5(R) therapies in severe asthma found that response was mainly predicted by indicators of good baseline disease control. However, long-term response predictors remain unclear.

Methods: Responders to anti-IL-5/IL-5(R) therapy in the well-characterised, real-life, international German Asthma Net (GAN) registry were analysed using regression analyses. Response was defined by ≥50% reduction in exacerbations or corticosteroid dose, super-response by a complete stop of both, and remission additionally by controlled asthma (ACT score≥20).

Results: Seventy-seven percent of 347 patients (55% female, 56.6±12.3 years, follow-up 20.3±13 months) were responders and showed improved exacerbation rates, asthma control, and corticosteroid treatment reduction. Response was independently predicted by inhaled corticosteroid dose (odds ratio [OR] 1.5; p = 0.014), exacerbation rate (OR 1.2; p = 0.009), and treatment duration (OR 1.05, p = 0.023). Univariately, blood eosinophil counts notably predicted response (OR 12.4; p = 0.004). Super-response was inversely associated with corticosteroid dependence and depression. Remission was associated with the absence of systemic corticosteroids, better asthma control, and FEV1 in litre.

Conclusions: These results underscore that long-term anti-IL-5/IL-5(R) therapy reduces exacerbation and corticosteroid burden, especially in patients with severe disease and high type 2 inflammatory burden. Contrastingly, low baseline corticosteroid use and markers of good asthma control predicted remission and super-responder status.