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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with limited treatment options. Despite the approval of pirfenidone and nintedanib that slow disease progression, IPF remains a disease with poor survival. Promising therapeutic candidates were tested as potential treatments for IPF and while some drugs were successful in phase II clinical trials, their successful transition to positive phase III was unfortunately disappointing. This highlights the "regression to the truth" concept in drug development, whereby positive phase II trial results may simply be a statistical anomaly rather than the result of true efficacy. We examine three pivotal trials of novel IPF therapies, zinpentraxin alfa, ziritaxestat and pamrevlumab, that failed in late-stage clinical development. These failures underscore common pitfalls in IPF drug development, including inadequate phase II sample sizes, reliance on surrogate endpoints like forced vital capacity, and challenges integrating background antifibrotic therapies. Moving forward, innovative approaches like adaptive trial designs, Bayesian statistics and composite endpoints could improve trial robustness. Moreover, platform trials may accelerate drug development by testing multiple therapies simultaneously. Negative trials are not failures but opportunities for learning. By recognising and addressing these challenges, while also embracing novel trial methodologies, we can enhance drug development and improve IPF outcomes.

Radiological imaging is a cornerstone in the clinical workup of lung diseases. Radiomics represents a significant advancement in clinical lung imaging, offering a powerful tool to complement traditional qualitative image analysis. Radiomic features are quantitative and computationally describe shape, intensity, texture and wavelet characteristics from medical images that can uncover detailed and often subtle information that goes beyond the visual capabilities of radiological examiners. By extracting this quantitative information, radiomics can provide deep insights into the pathophysiology of lung diseases and support clinical decision-making as well as personalised medicine approaches. In this educational review, we provide a step-by-step guide to radiomics-based medical image analysis, discussing the technical challenges and pitfalls, and outline the potential clinical applications of radiomics in diagnosing, prognosticating and evaluating treatment responses in respiratory medicine.

Prescribing the optimal combination of anti-tuberculosis drugs at the right dose is a fundamental step to achieve successful treatment outcomes. To aid the decision, clinicians should consider multiple factors, such as body weight, age, results of drug susceptibility testing, risk of intolerance and potential drug-drug interactions. In this viewpoint, we outline different aspects of dose selection in the treatment of tuberculosis (TB) such as traditional pharmacokinetics/pharmacodynamics, population pharmacokinetics models, the importance of real-world evidence and clinical trial design in the development of shorter treatment regimens and the new TB drug pipeline. Therapeutic drug monitoring for rifampicin, linezolid and amikacin may significantly improve their risk-benefit profile promoting their responsible administration. Precision dosing of novel, repurposed or conventional TB drugs should ensure optimal efficacy, while minimising toxicity and the development of resistance.

Breathlessness, or dyspnoea, is a complex symptom influenced by respiratory, cardiovascular and neural mechanisms, necessitating a systematic and tiered approach for accurate diagnosis and effective management. This review presents a structured, three-tier diagnostic framework, comprising history-taking, static testing (such as pulmonary function tests and thoracic imaging), and dynamic testing (e.g., 6-minute walk test and cardiopulmonary exercise testing) for comprehensive assessment. Each tier is designed to progressively investigate and characterise underlying conditions. This framework is specifically tailored for use in an outpatient general respiratory clinic setting, where clinicians evaluate chronic or unexplained dyspnoea in non-acute patients. Literature and guidelines support this approach, highlighting the importance of combining clinical examination, imaging, laboratory testing and dynamic assessments to capture both static and exertional components of dyspnoea. Emphasising a patient-centred approach, this framework aims to improve diagnostic accuracy and guide targeted therapeutic interventions.

Pulmonary vasculopathy presents as a spectrum of diseases affecting the precapillary pulmonary arterioles, the capillaries and the venules. Pulmonary veno-occlusive disease (PVOD) is classified under group 1 pulmonary arterial hypertension (PAH) as subgroup 1.5 (PAH with features of capillary/venous involvement), and represents a progressive and fatal spectrum of pulmonary vascular disorders. PVOD and pulmonary capillary haemangiomatosis (PCH) can be clinically indistinguishable and often coexist, along with the same risk factors and genetic alterations; they are referred to together as PVOD/PCH in the literature. For brevity, we use the clinical term PVOD in this article. PVOD cannot be distinguished from other forms of PAH based on symptoms and haemodynamics. Risk factors include exposure to toxins/chemotherapeutic drugs and genetic mutation in the EIF2AK4 gene. Radiographic features such as mediastinal adenopathy, centrilobular ground-glass opacities, and interlobular septal thickening, along with the presence of hypoxia and reduced diffusion capacity of the lung may be required for a clinical diagnosis of PVOD, as lung biopsy carries a high risk for bleeding. Characteristic histological findings include narrowing/occlusion of small pulmonary veins. The development of pulmonary oedema with pulmonary vasodilator therapy limits therapeutic options for PVOD. With limited treatment options, lung transplantation remains the only curative treatment.

Group 3 pulmonary hypertension (PH) associated with lung disease is a common cause of PH and is associated with substantial morbidity and mortality. Multiple studies of pulmonary arterial hypertension (PAH) therapies in this population have demonstrated conflicting results regarding their safety and efficacy, and therefore the optimum treatment for this group is unknown. The INCREASE and PERFECT randomised, double-blind, placebo-controlled trials attempted to address this unmet need by exploring the role of inhaled treprostinil (iTRE) in PH associated with interstitial lung disease (PH-ILD) and PH associated with COPD (PH-COPD), respectively. In the INCREASE and PERFECT studies individuals were randomised to placebo or iTRE, which was administered via an ultrasonic, pulsed-delivery nebuliser to a maximum dose of 72 μg, four times a day. The INCREASE study randomised 326 subjects with PH-ILD over a 16-week period and met its primary endpoint of change in 6-min walk distance, with a treatment effect of +31.12 m (p<0.001). Reduced disease progression events and increased forced vital capacity were also reported in the treatment arm in a post hoc analysis. By contrast, the PERFECT study was stopped prematurely by the data and safety monitoring committee due to evidence that iTRE increased serious adverse events in subjects with PH-COPD. This journal club provides an overview of these important trials and highlights pertinent unanswered questions in this field.

Secondary pneumothoraces can be the first presentation of pleural malignancies and may also complicate their course. They are often associated with prolonged air leaks, and cardiothoracic intervention can be required. https://bit.ly/3DEvPem.

Background: Tuberculosis (TB) remains a significant global health challenge despite ongoing control efforts, particularly in the context of drug-resistant TB (DR-TB), where treatment success rates remain low, underscoring the need for new therapeutic options. This review synthesises current evidence, since the publication of the World Health Organization guidelines in 2022, on the safety and efficacy of existing and new regimens for drug-susceptible TB (DS-TB) and DR-TB in adults and children.

Methods: A comprehensive search was performed across three databases for studies published between January 2022 and February 2024, focusing on current and new TB treatment regimens. Additional backward and forward citation searches were conducted to identify relevant literature.

Results: 35 studies were included, evaluating the efficacy, safety and economic impact of new oral regimens for DS-TB and DR-TB. Regimens based on bedaquiline or delamanid demonstrated high success rates and good tolerability. The BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) regimen was more effective and safer than the standard care, while shorter DR-TB regimens reduced costs and increased success rates. However, shorter regimens for DS-TB were associated with increased drug costs. Though limited, paediatric studies suggest that shorter, safer regimens may benefit children.

Conclusion: Evidence supports the adoption of shorter treatment regimens for both DR-TB and DS-TB to improve safety, effectiveness and cost-effectiveness, particularly in resource-limited settings.

A 40-year-old woman begins to have breathing difficulties after a history of ophthalmological issues. She then has a complex and complicated clinical course with multiple interesting diagnoses and treatments, with much to be learnt along the way. https://bit.ly/4gIolF8.

Explore how collaborations between academics and lung health support groups can enhance social connections in chronic disease care. Read this viewpoint for insights relevant to researchers, directly from those involved. #LungHealth#Academicpartnership https://bit.ly/4ggrwE0.