Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort.

BACKGROUND: Low lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV1), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population. METHODS AND FINDINGS: From the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV1 with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV1 (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > -1 SD), 19% (n = 4,353) moderate (z-score -1 to > -2 SD), and 6% (n = 1,329) severely low FEV1 (z-score = < -2 SD). There was a graded association between lower FEV1 with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV1 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV1 with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred. CONCLUSIONS: We observed graded associations between lower FEV1 with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

The role of eosinophils in sepsis and acute respiratory distress syndrome: a scoping review.

PURPOSE: Septic shock and acute respiratory distress syndrome (ARDS) are characterized by a dysregulated immune host response that may respond to steroid therapy. Eosinophils contribute to type 2 inflammation that often responds to steroid therapy; their role in immune dysregulation and outcomes in sepsis and ARDS is unclear. SOURCE: A systematic search of Cochrane Library, MEDLINE, and EMBASE was performed from inception to 9 September 2020. The search comprised the following terms: eosinophils, sepsis, septic shock, and ARDS. Two reviewers independently screened abstracts and texts and extracted data on disease severity and clinical outcomes. PRINCIPAL FINDINGS: Thirty-nine studies were identified: 30 evaluated serum eosinophil count in sepsis, one evaluated eosinophil activity in sepsis, three assessed bronchoalveolar lavage (BAL) eosinophil count in ARDS, four assessed eosinophil activity in ARDS, and one assessed peripheral eosinophil count in ARDS. Eleven studies showed an association between eosinopenia and sepsis, and eight studies found persistent eosinopenia at > 48 hr of intensive care unit admission to predict mortality and readmission in septic patients. Three studies found BAL eosinophil count to be low in ARDS, although one found that levels rose in late-phase ARDS. Three studies found eosinophil activity markers in BAL to be high in ARDS and correlate with ARDS severity. CONCLUSION: Persistent peripheral eosinopenia is a marker of bacterial sepsis and is independently associated with poor outcomes. Bronchoalveolar lavage eosinophil counts are low in early-phase ARDS, but increase in late-phase ARDS, while elevated markers of eosinophil activity correlate with ARDS severity. Further studies understanding the mechanisms leading to eosinopenia in sepsis and increased eosinophil activity in ARDS are needed.

RéSUMé: OBJECTIF: Le choc septique et le syndrome de détresse respiratoire aiguë (SDRA, ARDS en anglais) se caractérisent par une réponse immunitaire dérégulée chez l'hôte qui pourrait répondre à une corticothérapie. Les éosinophiles contribuent à l'inflammation de type 2, laquelle répond souvent à la corticothérapie; leur rôle dans la dérégulation immunitaire et les devenirs en cas de sepsis et de SDRA n'est pas clair. SOURCE: Une recherche systématique dans les bases de données Cochrane Library, MEDLINE et EMBASE a été réalisée de leur création au 9 septembre 2020. La recherche comprenait les termes suivants : éosinophiles, sepsis, choc septique et SDRA. Deux réviseurs ont examiné de manière indépendante les résumés et textes et ont extrait les données décrivant la gravité de la maladie et les devenirs cliniques. CONSTATATIONS PRINCIPALES: Trente-neuf études ont été identifiées : 30 études portaient sur le décompte d'éosinophiles sériques lors de sepsis, une étude examinait l'activité des éosinophiles dans un contexte de sepsis, trois ont évalué le décompte d'éosinophiles par lavage bronchoalvéolaire (LBA) dans les cas de SDRA, quatre ont examiné l'activité des éosinophiles dans le SDRA, et une a évalué le décompte d'éosinophiles périphériques dans les cas de SDRA. Onze études ont montré une association entre l'éosinopénie et le sepsis, et huit études ont remarqué qu'une éosinopédie persistante pour plus de 48 heures après l'admission à l'unité de soins intensifs était un prédicteur de mortalité et de réadmission chez les patients septiques. Trois études ont révélé que le nombre d'éosinophiles dans un LBA était faible en cas de SDRA, bien qu'une étude ait constaté que les taux augmentaient dans les SDRA de phase tardive. Trois études ont révélé que les marqueurs d'activité éosinophilique dans les LBA étaient élevés dans les cas de SDRA et étaient corrélés à la gravité du SDRA. CONCLUSION: L'éosinopénie périphérique persistante est un marqueur de sepsis bactérien et est indépendamment associée à de mauvais pronostics. Les décomptes d'éosinophiles dans les lavages bronchoalvéolaires sont bas dans les cas de SDRA en phase précoce, mais augmentent dans le SDRA en phase tardive, alors que des marqueurs élevés d'activité éosinophilique sont corrélés à la sévérité du SDRA. D'autres études visant à comprendre les mécanismes menant à l'éosinopénie dans le sepsis et à l'augmentation de l'activité éosinophilique dans le SDRA sont nécessaires.

Pulmonary rehabilitation in interstitial lung diseases.

PURPOSE OF REVIEW: This review will provide an overview of the components and current evidence to support pulmonary rehabilitation in patients with interstitial lung diseases (ILD), focusing on the latest findings in enhancing quality of life and functional capacity using exercise training and education. RECENT FINDINGS: Recent literature demonstrates a longer duration of pulmonary rehabilitation results in sustained improvements in functional capacity and quality of life in patients with ILD. Educational components tailored to ILD provide added value to supervised exercise training. Enhancing exercise training with hyperoxia merits further study and other modalities such as pursed-lip breathing have been shown to be counterproductive. SUMMARY: Recent evidence continues to support the use of tailored pulmonary rehabilitation programs in patients with ILD. Areas which require further investigation include identifying optimal exercise training regimens, educational topics, and breathing techniques that are specifically designed for ILD.

Conducting Prospective Research as a Trainee: Experiences with the DRIVE-SAFE Study.

Conducting clinical research during a 2-year critical care fellowship is a challenging endeavor. Fellows are often met with multiple barriers when considering clinical research projects during fellowship, including time, mentorship, resources, and clinical support. This paper presents the perspective and experiences of a group of critical care fellows who conducted the DRIVE-SAFE (Driving Pressure in Assisted Ventilation as a Predictor for Successful Liberation from Invasive Mechanical Ventilation) feasibility study, which aimed to determine measurable physiological variables that could be associated with lung injury and affect duration of mechanical ventilation. This paper provides a guide for trainees on how to conduct prospective clinical research at the bedside. We describe three key steps, including formulating a research question, developing appropriate methodology, and establishing outcomes. We also present the challenges that trainees may encounter when conducting prospective studies and how to overcome these challenges with proper mentorship, training, and collaboration with key stakeholders. These perspectives may provide useful guidance for current and future trainees interested in conducting prospective clinical research at the bedside.

Trajectories and Prognostic Significance of 6-Minute Walk Test Parameters in Fibrotic Interstitial Lung Disease: A Multicenter Study.

BACKGROUND: Functional capacity, as measured by the 6-min walk test (6MWT), is often reduced in fibrotic interstitial lung disease (ILD). This study evaluated longitudinal changes and the prognostic significance of 6MWT parameters, and explored change in oxygenation status as a physiological criterion to define disease progression in patients with fibrotic ILD. RESEARCH QUESTIONS: What are the trajectories and prognostic value of 6MWT parameters in patients with fibrotic ILD? STUDY DESIGN AND METHODS: Using prospective registries in Australia and Canada, patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD were stratified by the presence of criteria for progressive pulmonary fibrosis (PPF). The cumulative incidence of exertional and resting hypoxemia and changes in 6-min walk distance (6MWD) and composite indices (distance-saturation product and distance-saturation-oxygen product) were determined, with prognostic significance evaluated at the time of meeting criteria for PPF. New-onset exertional or resting hypoxemia was evaluated as another potential criterion for PPF. RESULTS: Patients with IPF/PPF (n = 126) and non-IPF/PPF (n = 227) had a similar cumulative incidence of exertional hypoxemia and annualized decline in 6MWD and composite indices, which varied across each PPF criterion. Patients with IPF/non-PPF (n = 231) and non-IPF/non-PPF (n = 531) had a significantly lower incidence of hypoxemia than those with IPF/PPF, with an annualized increase in 6MWD and composite indices in the non-IPF/non-PPF group. Exertional or resting hypoxemia at the time of meeting criteria for PPF was independently associated with reduced transplant-free survival in IPF and non-IPF, adjusting for patient demographics and lung function. Adding new-onset exertional or resting hypoxemia as a physiological criterion reduced the median time to development of PPF from 11.2 to 6.7 months in IPF and from 11.7 to 5.6 months in non-IPF in patients who eventually met both definitions (P < .001 for both). INTERPRETATION: Patients with IPF/PPF and non-IPF/PPF have comparable deterioration in functional capacity. Oxygenation status provides prognostic information in PPF and may assist in defining disease progression in fibrotic ILD.