Acute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 international working group report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AE. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to DAD in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.

Asthma is a heterogeneous disease affecting nearly 300 million people around the world. It is the most common chronic respiratory disease of childhood. There are significant sex differences in asthma incidence, severity, and morbidity around the time of puberty. The reasons for these peri-pubertal changes around the time of puberty are still not fully understood but they are likely multifactorial. In this review, we will discuss several proposed contributing mechanisms, including sex differences in anatomy and development, the effects of sex hormones on airway inflammation and reactivity, the immunomodulatory effects of sex hormones, differences in mucociliary function, and sex differences in genetic and epigenetic factors.

The advent of CFTR modulators is fundamentally reshaping people with cystic fibrosis (pwCF) care and research. Despite unprecedented improvements in lung function and predicted survival, a substantial proportion of pwCF continue to exhibit residual disease activity (RDA) across multiple biological and clinical domains. Persistent abnormalities in CFTR function, mucus properties, mucociliary clearance, airway infection, inflammation and symptom burden indicate that CFTR modulation does not fully normalize airway physiology or eliminate the pathological processes underlying CF lung disease. This review proposes RDA as a conceptual framework for identifying ongoing, potentially modifiable disease processes in people receiving CFTR modulators. Candidate measures across complementary mechanistic and clinical domains are examined, and their potential multidimensional interpretation as a means of supporting more individualized monitoring and treatment decisions is discussed. We consider the implications of RDA for clinical research by identifying key evidence gaps, outlining a stepwise pathway for its definition and validation. We further explore the potential to inform sensitive endpoint selection, enrich study populations and guide the development of therapies targeting disease processes that persist despite CFTR modulation. As the CF population ages and disease trajectories evolve, care models and research priorities must move beyond conventional measures of disease severity alone. A better understanding and systematic evaluation of RDA may help align long-term clinical management and future trial design with the changing needs of people with CF, while ensuring that therapeutic advances translate into sustained health gains.