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Nasal nitric oxide concentrations are extremely low in primary ciliary dyskinesia (PCD), and measurement of this nasal gas is recommended as a PCD diagnostic test in cooperative patients aged 5 years and older. However, nasal nitric oxide measurements must be performed with chemiluminescence analyzers using a standardized protocol to ensure proper results, because nasal nitric oxide values can be influenced by various internal and external factors. Repeat nasal nitric oxide testing on separate visits is required to ensure that low diagnostic values are persistent and consistent with PCD. This technical paper presents the standard operating procedures for nasal nitric oxide measurement used by the PCD Foundation Clinical and Research Centers Network at various specialty centers across North America. Adherence to this document ensures reliable nasal nitric oxide testing and high diagnostic accuracy when employed in a population with appropriate clinical phenotypes for PCD.

The article highlights several medical research papers. Topics include the characterization of commercially available human primary alveolar epithelial cells, the role of farnesoid X receptor in protecting the lung against IL-6-induced ferroptosis, and the impact of alternative splicing on transcriptome diversity in chronic obstructive pulmonary disease . It emphasizes the importance of these studies in understanding lung physiology, disease mechanisms, and potential therapeutic strategies.

The article informs about highlighted papers by junior investigators in the American Journal of Respiratory Cell and Molecular Biology. The topics include the promotion of pulmonary fibrosis through the upregulation of NEAT1 by GOLM1, the amelioration of sepsis-associated lung injury through inducing IL-33-mediated type 2 immunity by lack of S1PR2 in macrophages, and the role of interstitial macrophages in mediating efferocytosis of alveolar epithelium during influenza infection.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.

The article focuses on various studies exploring mechanisms underlying lung diseases, specifically how airway smooth muscle (ASM) phenotype, unfolded protein responses, lung hematopoietic progenitors, and aging affect lung function and pathology. It identifies how excessive serum response factor (SRF) expression in ASM cells enables a dual contractile-proliferative phenotype, potentially worsening asthma.

The article presents the discussion on NIH news briefs. Topics include diverse functions of alveolar macrophages (AMØs) in the lung, highlighting their distinct roles during homeostasis and in response to lung injury such as O3 exposure; and controversy surrounding the recruitment of monocyte-derived AMØs in lung injury models, and the importance of efferocytosis in promoting resolution of inflammation.

The article offers information on bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, characterized by impaired lung development. Topics include the concept of dysanapsis in BPD, which refers to disproportionate airways and parenchymal size, and its contribution to late respiratory disease.

The use of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory failure (ARF) in adults is growing rapidly given recent advances in technology, even though there is controversy regarding the evidence justifying its use. Because ECMO is a complex, high-risk, and costly modality, at present it should be conducted in centers with sufficient experience, volume, and expertise to ensure it is used safely. This position paper represents the consensus opinion of an international group of physicians and associated health-care workers who have expertise in therapeutic modalities used in the treatment of patients with severe ARF, with a focus on ECMO. The aim of this paper is to provide physicians, ECMO center directors and coordinators, hospital directors, health-care organizations, and regional, national, and international policy makers a description of the optimal approach to organizing ECMO programs for ARF in adult patients. Importantly, this will help ensure that ECMO is delivered safely and proficiently, such that future observational and randomized clinical trials assessing this technique may be performed by experienced centers under homogeneous and optimal conditions. Given the need for further evidence, we encourage restraint in the widespread use of ECMO until we have a better appreciation for both the potential clinical applications and the optimal techniques for performing ECMO.

In a previous study of older pulp and paper workers in Berlin, New Hampshire, decrements in spirometry results associated with accidental exposures to high levels of irritant gases depended on cumulative levels of pulp mill exposure and cigarette smoking. Many of those subjects were older and retired. A new study was initiated to assess whether gassing events were a problem among current workers. Three hundred white male pulp and paper workers from the mill in Berlin, New Hampshire, were surveyed in 1992. Testing included spirometry and questionnaires. The mean age was 40.4 yr, and the mean tenure with the company was 18.5 yr. A total of 105 of the 300 subjects (35%) reported ever having an episode of high exposure to chlorine gases (i.e., being gassed). The percentage gassed was 51% for pulp mill workers and only 13% for other employees. For subjects with no more than 26 pack-years of cigarette smoking, obstruction (i.e., abnormally low FEV1 and FEV1/FVC) was observed only among those with a history of gassing. Also, the combination of high cigarette smoking (i.e., > 26 pack-years) and gassing had a greater than additive effect on obstruction. These findings suggest that additional controls are needed to minimize the number of gassing events in this and other chemical pulp mills.

The article reveals that RAGE (receptor for advanced glycation end products) is a receptor for the SARS-CoV-2 N protein, as reported by Jie Xia and colleagues. Topics include evaluating novel protein phosphatase 2A (PP2A) activators for emphysema treatment, with Brian Soto and colleagues introducing a stable PP2A activator, ATUX-792, showing promising effects in models of smoke-induced and AAT deficiency-associated emphysema.

An editorial is presented by the outgoing Editor of the Journal, reflecting on the past 7 years of service, achievements, and challenges. Topics include enhancing the quality and impact of the Journal, addressing emerging issues like Open Access mandates and the influence of artificial intelligence in academic publishing, and the importance of diversity and scientific integrity in journal operations.

The article discusses the results of two medical studies. A study by Joseph Farahany and colleagues examined the role of CD38, an ectoenzyme expressed in macrophages, to the regulation of NLRP3 inflammasome to prevent endotoxemic lung injury. A study led by Broa Coates, Clarissa Koch and Andrew Prigge investigated host response to SARS-CoV-2 in the nasal mucosa using RNA sequencing to determine if age-related differences in the initial response to SARS-CoV-2 may impact disease severity.

The article presents the discussion on original papers and reviews and an increasing number of high-quality research letters often pilot or early studies. Topics include highlighting asthma, interstitial lung disease, and critical care reflecting in the rising impact factor; and assisted by production of podcasts and animated videos together with engaging readers on social media.

The article focuses on the use of cluster analysis in severe asthma research to identify patient phenotypes for personalized treatment. It highlights the problem of circular analysis, where hypotheses are generated and tested on the same dataset, leading to inflated Type 1 error rates. It study reviews influential asthma clustering papers and finds that a significant percentage of statistical tests involve circular reasoning, suggesting more overlap in clusters than reported.

This document is a reply to concerns raised by Dr. Taito and colleagues regarding a recent paper on an improved active mobilization program for critically ill patients with diabetes. The authors clarify that all patients randomized in the main trial were included in the analysis, contrary to the concern that the high-dose early mobilization group did not include all eligible patients. They also explain that the duration of mobilization was not assessed to avoid violating the intention-to-treat principle. The authors provide additional information on mobilization and metabolic variables in patients with and without diabetes. They acknowledge the need for a dose-response analysis, which is currently in progress. [Extracted from the article]

Repeated exposure to chlorine in pulp mills and paper can induce persistent asthma-like symptoms such as bronchial hyperresponsiveness and variable changes in airway caliber. The long-term time course of bronchial hyperresponsiveness has not been examined. We studied 20 of 29 subjects (69% participation rate) who demonstrated bronchial hyperresponsiveness to methacholine when they were first assessed, 18 to 24 mo after repeatedly inhaling "puffs" of high concentrations of chlorine in a paper mill over a 3-mo period. Each subject answered a respiratory questionnaire and underwent spirometry and a methacholine inhalation test 12 mo after the initial survey, 30 to 36 mo after the chlorine inhalations. Three subjects required inhaled steroids at the time of the initial survey and three at the time of the second, including two who carried on using these preparations. Only one subject changed smoking habits. There were no significant overall changes in FEV1 on the two occasions, nine subjects having a FEV1 < 80% on the first occasion and eight on the second. Six of the 18 subjects (33%) who underwent a methacholine inhalation test on both occasions had significantly improved PC20 results, including five for whom the PC20 value was within the normal range. All six subjects had normal FEV1 values on both assessments. Although changes in spirometry induced by repeated exposure to chlorine seem to persist, bronchial hyperresponsiveness can improve significantly in those with normal airway caliber. This suggests that less pronounced bronchial alterations induced by repeated exposures to chlorine may be reversible.

The article highlights the potential applications of Large Language Models (LLMs) in health services research, discussing their role in expanding background knowledge, determining study design, collecting and analyzing data, and disseminating findings. It emphasizes the need for researchers to understand and effectively utilize LLMs, while also cautioning against their limitations and potential risks.

Background: In 2008, a dedicated American Thoracic Society/European Respiratory Society task force published a paper on the possible use and limitations of clinical outcomes and biomarkers to evaluate the impact of pharmacological therapy in patients with chronic obstructive pulmonary disease. Since then, our scientific understanding of chronic obstructive pulmonary disease has increased considerably; there has been a progressive shift from a one-size-fits-all diagnostic and therapeutic approach to a personalized approach; and many new treatments currently in development will require new endpoints to evaluate their efficacy adequately. Objectives: The emergence of several new relevant outcome measures motivated the authors to review advances in the field and highlight the need to update the content of the original report. Methods: The authors separately created search strategies for the literature, primarily based on their opinions and assessments supported by carefully chosen references. No centralized examination of the literature or uniform criteria for including or excluding evidence were used. Measurements and Main Results: Endpoints, outcomes, and biomarkers have been revisited. The limitations of some of those reported in the American Thoracic Society/European Respiratory Society task force document have been highlighted. In addition, new tools that may be useful, especially in evaluating personalized therapy, have been described. Conclusions: Because the "label-free" treatable traits approach is becoming an important step toward precision medicine, future clinical trials should focus on highly prevalent treatable traits, and this will influence the choice of outcomes and markers to be considered. The use of the new tools, particularly combination endpoints, could help better identify the right patients to be treated with the new drugs. [ABSTRACT FROM AUTHOR]

ICU clinicians rely on bedside physiological measurements to inform many routine clinical decisions. Because deranged physiology is usually associated with poor clinical outcomes, it is tempting to hypothesize that manipulating and intervening on physiological parameters might improve outcomes for patients. However, testing these hypotheses through mathematical models of the relationship between physiology and outcomes presents a number of important methodological challenges. These models reflect the theories of the researcher and can therefore be heavily influenced by one’s assumptions and background beliefs. Model building must therefore be approached with great care and forethought, because failure to consider relevant sources of measurement error, confounding, coupling, and time dependency or failure to assess the direction of causality for associations of interest before modeling may give rise to spurious results. This paper outlines the main challenges in analyzing and interpreting these models and offers potential solutions to address these challenges. [ABSTRACT FROM AUTHOR]

The article focuses on expressing gratitude to the international respiratory community for their overwhelming response to the call for papers on chronic obstructive pulmonary disease (COPD), leading to the creation of a second issue with a strong emphasis on COPD content. It authors highlight the exciting advancements in COPD research, with a growing understanding of key biological pathways and the potential for new therapeutics in the field.

Background: Patients who survive critical illness have well-defined physical, cognitive, emotional, and familial problems. However, the impact of these problems on survivors' ability to return to work and other financial outcomes is less clear.Objectives: To determine the financial and employment consequences of an intensive care stay, we performed a systematic review and meta-analysis.Data Sources: We searched the MEDLINE, Embase, and CINAHL databases (1970-2018). All publication types except narrative reviews, case reports, case-control studies, and editorials were included. Included studies assessed financial outcomes in patients admitted to critical care and their caregivers.Data Extraction: Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome reported was return to employment among those previously employed. We also examined financial stress and the impact financial outcomes had on quality of life and psychosocial health.Data Synthesis: Of 5,765 eligible abstracts, 51 studies were included, which provided data on 858 caregivers/family members and 7,267 patients. Forty-two papers reported patient outcomes, and 11 papers described caregivers/family members. Two papers included data from both patients and caregivers/family members. Return to employment was the most commonly reported financial outcome for critical care survivors. The pooled estimates for return to employment among those who were employed before critical illness were 33% (95% confidence interval [CI], 21-48%), 55% (95% CI, 45-64%), and 56% (95% CI, 45-66%) at 3, 6, and 12 months, respectively. Across the studies included in this review, there was a positive association with psychosocial health if patients returned to employment. This included improved health-related quality of life and fewer depressive symptoms. Regarding caregivers/family members, six studies reported changes in employment such as reduced hours and lost earnings.Conclusions: After critical illness, many patients who were previously employed do not return to work, even one year later. This new job loss is associated with worse health-related quality of life among survivors and worse psychological function among survivors and caregivers/family members. More interventional research is required to understand how best to support employability after critical illness.Registered with PROSPERO (CRD42018102360). [ABSTRACT FROM AUTHOR]

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities. [ABSTRACT FROM AUTHOR]