Associations of Personal Hourly Exposures to Air Temperature and Pollution with Resting Heart Rate in Chronic Obstructive Pulmonary Disease.

Previous studies linked higher daily ambient air temperature and pollution with increased cardiorespiratory morbidity, but immediate effects of personal, hourly exposures on resting heart rate remained unclear. We followed 30 older former smokers with chronic obstructive pulmonary disease (COPD) in Massachusetts for four nonconsecutive 30-day periods over 12 months, collecting 54,487 hourly observations of personal air temperature, fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and resting heart rate. We explored the single lag effects (0-71 h) and cumulative effects (0-5 h, the significant lag windows) of air temperature and pollution on resting heart rate using generalized additive mixed models with distributed lag nonlinear models. Single lag effects of higher air temperature and pollutants on higher resting heart rate were most pronounced at lag 0 to 5 h. Cumulative effects of higher air temperature, PM2.5, O3, and NO2 (each interquartile range increment) on higher resting heart rate at lag 0-5 h, show differences of (beats per minute [bpm], 95% CI) 1.46 (1.31-1.62), 0.35 (0.32-0.39), 2.32 (2.19-2.45), and 1.79 (1.66-1.92), respectively. In conclusion, higher personal hourly air temperature, PM2.5, O3, and NO2 exposures at lag 0-5 h are associated with higher resting heart rate in COPD patients.

Protocol for the air purification for eosinophilic COPD study (APECS): a randomised controlled trial of home air filtration by HEPA.

INTRODUCTION: Exposure to particulate matter (PM) pollution has been associated with lower lung function in adults with chronic obstructive pulmonary disease (COPD). Patients with eosinophilic COPD have been found to have higher levels of airway inflammation, greater responsiveness to anti-inflammatory steroid inhalers and a greater lung function response to PM pollution exposure compared with those with lower eosinophil levels. This study will evaluate if reducing home PM exposure by high-efficiency particulate air (HEPA) air filtration improves respiratory health in eosinophilic COPD. METHODS AND ANALYSIS: The Air Purification for Eosinophilic COPD Study (APECS) is a double-blinded randomised placebo-controlled trial that will enrol 160 participants with eosinophilic COPD living in the area of Boston, Massachusetts. Real and sham air purifiers will be placed in the bedroom and living rooms of the participants in the intervention and control group, respectively, for 12 months. The primary trial outcome will be the change in forced expiratory volume in 1 s (FEV1). Lung function will be assessed twice preintervention and three times during the intervention phase (at 7 days, 6 months and 12 months postrandomisation). Secondary trial outcomes include changes in (1) health status by St. George's Respiratory Questionnaire; (2) respiratory symptoms by Breathlessness, Cough and Sputum Scale (BCSS); and (3) 6-Minute Walk Test (6MWT). Inflammatory mediators were measured in the nasal epithelial lining fluid (NELF). Indoor PM will be measured in the home for the week preceding each study visit. The data will be analysed to contrast changes in outcomes in the intervention and control groups using a repeated measures framework. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Beth Israel Deaconess Medical Centre (protocol #2019P0001129). The results of the APECS trial will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION: NCT04252235. Version: October 2023.

"It's a cause I believe in": factors motivating participation and engagement in longitudinal, respiratory-focused research studies.

BACKGROUND: Key to the success of any prospective cohort study is the effective recruitment and retention of participants, but the specific factors that influence younger adults of the Millennial generation to participate in research are not well-understood. The objective of this qualitative study was to identify factors that motivated participation and engagement in longitudinal research studies focused on respiratory health among a diverse group of young adults. METHODS: We conducted qualitative, semi-structured interviews with 50 younger adult participants (aged 25-35 years) regarding factors influencing their participation in longitudinal research studies. Thematic analysis was used to develop, organize, and tabulate the frequency of key themes. In exploratory analyses, we examined for patterns in the distribution of key themes across racial, ethnic, or socioeconomic groups. RESULTS: Participants identified several key themes that affected their willingness to participate in longitudinal studies. These included the health-related benefits generated by research (both to the individual and to society at-large), factors related to the institution and study team conducting the research, concerns regarding unethical and/or unrepresentative study design, and barriers to participation in research. Certain factors may be more impactful to underrepresented groups, including concerns regarding data privacy and confidentiality. CONCLUSIONS: In this diverse group of younger adults, we identified specific factors that motivated participation and predicted high engagement in longitudinal research studies focused on respiratory health. Implementing and integrating these factors into study protocols may improve recruitment and retention, including among participants who are historically underrepresented in research.

Personal and community-level exposure to air pollution and daily changes in respiratory symptoms and oxygen saturation among adults with COPD.

Background: Air pollution exposure is associated with hospital admissions for Chronic Obstructive Pulmonary Disease (COPD). Few studies have investigated whether daily personal exposure to air pollutants affects respiratory symptoms and oxygenation among COPD patients. Methodology: We followed 30 former smokers with COPD for up to 4 non-consecutive 30-day periods in different seasons. Participants recorded worsening of respiratory symptoms (sub-categorized as breathing or bronchitis symptoms) by daily questionnaire, and oxygen saturation by pulse oximeter. Personal and community-level exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) were measured by portable air quality monitors and stationary monitors in the Boston area. We used generalized and multi-level linear mixed-effects models to estimate associations of the 24-hour average of each pollutant in the previous day with changes in respiratory symptoms and oxygen saturation. Results: Higher community-level exposure to air pollutants was associated with worsening respiratory symptoms. An interquartile range (IQR) higher community-level O3 was associated with a 1.35 (95%CI: 1.07-1.70) higher odds of worsening respiratory symptoms. The corresponding ORs for community-level PM2.5 and NO2 were 1.18 (95%CI: 1.02-1.37) and 1.06 (95%CI: 0.90-1.25), respectively. Community-level NO2 was associated with worsening bronchitis symptoms (OR=1.25, 95%CI: 1.00-1.56), but not breathing symptoms. Personal PM2.5 exposure was associated with lower odds of worsening respiratory symptoms (OR=0.91; 95%CI: 0.81-1.01). Personal exposure to NO2 was associated with 0.11% lower oxygen saturation (95%CI: -0.22, 0.00) per IQR. Conclusions: In this COPD population, there was a pattern of worsening respiratory symptoms associated with community-level exposure to O3 and PM2.5, and worsening oxygenation associated with personal exposure to NO2.

Differences of the Nasal Microbiome and Mycobiome by Clinical Characteristics of COPD Patients.

Rationale: While studies suggest that the lung microbiome may influence risk of chronic obstructive pulmonary disease (COPD) exacerbations, little is known about the relationship between the nasal biome and clinical characteristics of COPD patients. Methods: We sampled the nasal lining fluid by nasosorption of both nares of 20 people with moderate-to-severe COPD. All 40 samples, plus 4 negative controls, underwent DNA extraction, and 16SV4 ribosomal RNA (rRNA) (bacterial) and ribosomal internal transcribed spacer 2 (ITS2) (fungal) sequencing. We measured the proportion of variance (R2) in beta diversity explained by clinical factors, including age, sex, body mass index (BMI), COPD treatment, disease severity (forced expiratory volume in 1 second [FEV1], symptom/exacerbation frequency), peripheral eosinophil level (≥150 versus <150 cells/µL) and season of sampling, with the PERMANOVA test on the Bray-Curtis dissimilarities, accounting for within-person correlation of samples. We assessed the relative abundance of microbial features in the nasal community and their associations with clinical characteristics using the Microbiome Multivariable Association with Linear Models (MaAsLin2) package. Results: The most abundant nasal fluid bacterial taxa were Corynebacterium, Staphylococcus, Streptococcus, Moraxella, and Dolosigranulum, and fungal taxa were Malassezia, Candida, Malasseziales, Cladosporium and Aspergillus. Bacterial microbiome composition was associated with short-acting muscarinic antagonist use (R2 11.8%, p=0.002), sex (R2 8.3%, p=0.044), nasal steroid use (R2 7.7%, p=0.064), and higher eosinophil level (R2 7.6%, p=0.084). Mycobiome composition was associated with higher eosinophil level (R2 14.4%, p=0.004) and low FEV1 (R2 7.5%, p=0.071). No specific bacterium or fungus differed significantly in relative abundance by clinical characteristics in the multivariate per-feature analysis. Conclusion: The taxonomical composition of the nasal biome is heterogeneous in COPD patients and may be explained in part by clinical characteristics.

The impact of personal and outdoor temperature exposure during cold and warm seasons on lung function and respiratory symptoms in COPD.

Rationale: Chronic obstructive pulmonary disease (COPD) patients often report aggravated symptoms due to heat and cold, but few studies have formally evaluated this. Methodology: We followed 30 Boston-based former smokers with COPD for four non-consecutive 30-day periods over 12 months. Personal and outdoor temperature exposure were measured using portable and Boston-area outdoor stationary monitors. Participants recorded daily morning lung function measurements as well as any worsening breathing (breathlessness, chest tightness, wheeze) and bronchitis symptoms (cough, sputum colour and amount) compared to baseline. Using linear and generalised linear mixed-effects models, we assessed associations between personal and outdoor temperature exposure (1-3-day moving averages) and lung function and symptoms, adjusting for humidity, smoking pack-years and demographics. We also stratified by warm and cold season. Results: Participants were on average 71.1±8.4 years old, with 54.4±30.7 pack-years of smoking. Each 5°C increase in personal temperature exposure was associated with 1.85 (95% CI 0.99-3.48) higher odds of worsening breathing symptoms. In the warm season, each 5°C increase in personal and outdoor temperature exposure was associated with 3.20 (95% CI 1.05-9.72) and 2.22 (95% CI 1.41-3.48) higher odds of worsening breathing symptoms, respectively. Each 5°C decrease in outdoor temperature was associated with 1.25 (95% CI 1.04-1.51) higher odds of worsening bronchitis symptoms. There were no associations between temperature and lung function. Conclusions: Our findings suggest that higher temperature, including outdoor exposure during the warm season and personal temperature exposure year-round, may worsen dyspnoea, while colder outdoor temperature may trigger cough and phlegm symptoms among COPD patients.

Vascular remodeling of the small pulmonary arteries and measures of vascular pruning on computed tomography.

Pulmonary hypertension is characterized histologically by intimal and medial thickening in the small pulmonary arteries, eventually resulting in vascular "pruning." Computed tomography (CT)-based quantification of pruning is associated with clinical measures of pulmonary hypertension, but it is not established whether CT-based pruning correlates with histologic arterial remodeling. Our sample consisted of 138 patients who underwent resection for early-stage lung adenocarcinoma. From histologic sections, we identified small pulmonary arteries and measured the relative area comprising the intima and media (VWA%), with higher VWA% representing greater histologic remodeling. From pre-operative CTs, we used image analysis algorithms to calculate the small vessel volume fraction (BV5/TBV) as a CT-based indicator of pruning (lower BV5/TBV represents greater pruning). We investigated relationships of CT pruning and histologic remodeling using Pearson correlation, simple linear regression, and multivariable regression with adjustment for age, sex, height, weight, smoking status, and total pack-years. We also tested for effect modification by sex and smoking status. In primary models, more severe CT pruning was associated with greater histologic remodeling. The Pearson correlation coefficient between BV5/TBV and VWA% was -0.41, and in linear regression models, VWA% was 3.13% higher (95% CI: 1.95-4.31%, p < 0.0001) per standard deviation lower BV5/TBV. This association persisted after multivariable adjustment. We found no evidence that these relationships differed by sex or smoking status. Among individuals who underwent resection for lung adenocarcinoma, more severe CT-based vascular pruning was associated with greater histologic arterial remodeling. These findings suggest CT imaging may be a non-invasive indicator of pulmonary vascular pathology.

Ambient air pollution exposure and radiographic pulmonary vascular volumes.

Exposure to higher levels of ambient air pollution is a known risk factor for cardiovascular disease but long-term effects of pollution exposure on the pulmonary vessels are unknown. METHODS: Among 2428 Framingham Heart Study participants who underwent chest computed tomography (CT) between 2008 and 2011, pulmonary vascular volumes were calculated by image analysis, including the total vascular volume and small vessel volume (cross-sectional area <5 mm2; BV5 defined as small vessel volume). Using spatiotemporal models and participant home address, we assigned 1-year (2008) and 5-year (2004-2008) average concentrations of fine particulate matter (PM2.5), elemental carbon (EC), and ground-level ozone (O3), and distance to major roadway. We examined associations of 1- and 5-year exposures, and distance to road, with CT vascular volumes using multivariable linear regression models. RESULTS: There was a consistent negative association of higher O3 with lower small vessel volumes, which persisted after adjustment for distance to road. Per interquartile range (IQR) of 2008 O3, BV5 was 0.34 mL lower (95% confidence intervals [CI], -0.61 to -0.06; P = 0.02), with similar results for 5-year exposure. One-year EC exposure and closer proximity to road were weakly associated with small vessel volumes; BV5 was 0.18 mL higher per IQR of 2008 EC (95% CI, -0.05 to 0.42; P = 0.13) and 0.40 mL higher per IQR closer proximity to road (95% CI: -0.10 to 0.89; P = 0.12). PM2.5 was not associated with small vascular volumes; BV5 was 0.26 mL lower per IQR of 2008 PM2.5 (95% CI: -0.68 to 0.16; P = 0.22). CONCLUSIONS: Among community-dwelling adults living in the northeastern United States, higher exposure to O3 was associated with lower small pulmonary vessel volumes on CT.

Complete Endotracheal Tube Transection by Patient Bite: A Case Report and Algorithm for Fragment Identification and Extraction.

We describe a case of a complete endotracheal tube (ETT) transection due to patient bite. The patient was intubated for postoperative pneumonia; during weaning of sedation, the patient was unable to tolerate pressure support ventilation (PSV) due to agitation. Adaptive support ventilation (ASV) improved patient comfort substantially. During a routine Spontaneous Breathing Trial (SBT) on PSV, the patient bit through the ETT, resulting in complete transection and an unsecured 20-cm airway fragment. Utilizing a multidisciplinary approach, we provided respiratory support and performed nasopharyngolaryngoscopy (NPL) to identify and extract the foreign body. An algorithm for management of ETT fragment extraction is provided.

Vascular Pruning on CT and Interstitial Lung Abnormalities in the Framingham Heart Study.

BACKGROUND: Pulmonary vascular disease is associated with poor outcomes in individuals affected by interstitial lung disease. The pulmonary vessels can be quantified with noninvasive imaging, but whether radiographic indicators of vasculopathy are associated with early interstitial changes is not known. RESEARCH QUESTION: Are pulmonary vascular volumes, quantified from CT scans, associated with interstitial lung abnormalities (ILA) in a community-based sample with a low burden of lung disease? STUDY DESIGN AND METHODS: In 2,386 participants of the Framingham Heart Study, we used CT imaging to calculate pulmonary vascular volumes, including the small vessel fraction (a surrogate of vascular pruning). We constructed multivariable logistic regression models to investigate associations of vascular volumes with ILA, progression of ILA, and restrictive pattern on spirometry. In secondary analyses, we additionally adjusted for diffusing capacity and emphysema, and performed a sensitivity analysis restricted to participants with normal FVC and diffusing capacity. RESULTS: In adjusted models, we found that lower pulmonary vascular volumes on CT were associated with greater odds of ILA, antecedent ILA progression, and restrictive pattern on spirometry. For example, each SD lower small vessel fraction was associated with 1.81-fold greater odds of ILA (95% CI, 1.41-2.31; P < .0001), and 1.63-fold greater odds of restriction on spirometry (95% CI, 1.18-2.24; P = .003). Similar patterns were seen after adjustment for diffusing capacity for carbon monoxide, emphysema, and among participants with normal lung function. INTERPRETATION: In this cohort of community-dwelling adults not selected on the basis of lung disease, more severe vascular pruning on CT was associated with greater odds of ILA, ILA progression, and restrictive pattern on spirometry. Pruning on CT may be an indicator of early pulmonary vasculopathy associated with interstitial lung disease.

Change in Inhaler Use, Lung Function, and Oxygenation in Association with Symptoms in COPD.

Despite clinical guidelines for chronic obstructive pulmonary disease (COPD) patients to self-treat worsening respiratory symptoms with supplemental inhaler/nebulizer use, few studies have investigated if symptom changes are associated with differences in oxygenation, lung function, or self-treatment. A total of 26 former smokers (mean age 72.7 ±7.5 years; 57.7% female) with COPD (≥ Global Initiative for Chronic Obstructive Lung Disease Stage 2) were followed for up to 4 months, during which they recorded daily oxygenation, lung function, and inhaler/nebulizer use. Differences in these health measures were assessed in association with self-reported worsening symptoms and COPD exacerbations, as defined by validated questionnaire. We collected 2451 observations with spirometry and questionnaire data and identified 253 symptom days (10.3%) and 47 (1.92%) exacerbation days. In linear mixed effects models adjusted for age, sex, race, height, weight, and season, each respiratory symptom reported worse than baseline was associated with a 0.19 percentage point (95% CI -0.31 to -0.07) lower daily oxygen saturation (p=0.002). On major symptom days (defined as worse-than-baseline dyspnea, sputum purulence or sputum amount), oxygen saturation was 0.56 percentage points lower (95% CI -0.89 to -0.23, p=0.001) than days without increased major symptoms. We found no association of symptom days or exacerbations with forced expiratory volume in 1 second. There were 8 reports of increased inhaler/nebulizer use from baseline on symptom days (1.5% of 253). In this moderate-to-severe COPD population, worsening respiratory symptoms were common and associated with lower oxygenation. However, participants did not self-treat symptoms with increased inhaler/nebulizer use, which may suggest poor perceived clinical benefit from short-acting bronchodilators and a potential target for patient education.

Radiographic pulmonary vessel volume, lung function and airways disease in the Framingham Heart Study.

Radiographic abnormalities of the pulmonary vessels, such as vascular pruning, are common in advanced airways disease, but it is unknown if pulmonary vascular volumes are related to measures of lung health and airways disease in healthier populations.In 2388 participants of the Framingham Heart Study computed tomography (CT) sub-study, we calculated total vessel volumes and the small vessel fraction using automated CT image analysis. We evaluated associations with measures of lung function, airflow obstruction on spirometry and emphysema on CT. We further tested if associations of vascular volumes with lung function were present among those with normal forced expiratory volume in 1 s and forced vital capacity.In fully adjusted linear and logistic models, we found that lower total and small vessel volumes were consistently associated with worse measures of lung health, including lower spirometric volumes, lower diffusing capacity and/or higher odds of airflow obstruction. For example, each standard deviation lower small vessel fraction (indicating more severe pruning) was associated with a 37% greater odds of obstruction (OR 1.37, 95% CI 1.11-1.71, p=0.004). A similar pattern was observed in the subset of participants with normal spirometry.Lower total and small vessel pulmonary vascular volumes were associated with poorer measures of lung health and/or greater odds of airflow obstruction in this cohort of generally healthy adults without high burdens of smoking or airways disease. Our findings suggest that quantitative CT assessment may detect subtle pulmonary vasculopathy that occurs in the setting of subclinical and early pulmonary and airways pathology.

Cigarette Smoke Exposure and Radiographic Pulmonary Vascular Morphology in the Framingham Heart Study.

Rationale: Cigarette smoke exposure is a risk factor for many lung diseases, and histologic studies suggest that tobacco-related vasoconstriction and vessel loss plays a role in the development of emphysema. However, it remains unclear how tobacco affects the pulmonary vasculature in general populations with a typical range of tobacco exposure, and whether these changes are detectable by radiographic methods. Objectives: To determine whether tobacco exposure in a generally healthy population manifests as lower pulmonary blood vessel volumes and vascular pruning on imaging. Methods: A total of 2,410 Framingham Heart Study participants with demographic data and smoking history underwent volumetric whole-lung computed tomography from 2008 to 2011. Automated algorithms calculated the total blood volume of all intrapulmonary vessels (TBV), smaller peripheral vessels (defined as cross-sectional area <5 mm2 [BV5]), and the relative fraction of small vessels (BV5/TBV). Tobacco exposure was assessed as smoking status, cumulative pack-years, and second-hand exposure. We constructed multivariable linear regression models to evaluate associations of cigarette exposure and pulmonary blood vessel volume measures, adjusting for demographic covariates, including age, sex, height, weight, education, occupation, and median neighborhood income. Results: All metrics of tobacco exposure (including smoking status, pack-years, and second-hand exposure) were consistently associated with higher absolute pulmonary blood vessel volume, higher small vessel volume, and/or higher small vessel fraction. For example, ever-smokers had a 4.6 ml higher TBV (95% confidence interval [CI] = 2.9-6.3, P < 0.001), 2.1 ml higher BV5 (95% CI = 1.3-2.9, P < 0.001), and 0.28 percentage-point-higher BV5/TBV (95% CI = 0.03-0.52, P = 0.03) compared with never-smokers. These associations remained significant after adjustment for percent predicted forced expiratory volume in 1 second, cardiovascular comorbidities, and did not differ based on presence or absence of airflow obstruction. Conclusions: Using computed tomographic imaging, we found that cigarette exposure was associated with higher pulmonary blood vessel volumes, especially in the smaller peripheral vessels. Although, histologically, tobacco-related vasculopathy is characterized by vessel narrowing and loss, our results suggest that radiographic vascular pruning may not be a surrogate of these pathologic changes.

Distal radius fractures in older patients: is anatomic reduction necessary?

UNLABELLED: The relationship between radiographic and functional outcomes in older patients with distal radius fractures is controversial. We explored this relationship by assessing the influence of radiographic displacement and fracture comminution on the functional outcomes of these fractures. We also asked whether operative intervention and demographic factors (age, gender, duration of followup) influenced outcome. We examined 53 patients older than 55 years with distal radius fractures with various functional assessments: range of motion (ROM) and strength measurements, three subjective surveys (Disabilities of the Arm, Shoulder, and Hand; Patient-rated Wrist Evaluation; Modernized Activity Subjective Survey of 2007), a Gartland and Werley score, and an objective, standardized hand performance test (Jebsen-Taylor). We measured angulation, articular gap/stepoff, and radial shortening on final radiographs and fracture comminution of preoperative radiographs. We observed no effect of radiographic displacement on subjective or objective outcome assessments, including standardized hand performance timed testing. Surgically treated fractures were less likely to display residual dorsal angulation and radial shortening, but surgical intervention did not independently predict functional outcome. Fracture comminution, patient gender, and months of followup similarly had no effect on outcome. We found no relationship between anatomic reduction as evidenced by radiographic outcomes and subjective or objective functional outcomes in this older patient cohort. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.