Health effects of filtering facepiece respirators: Research and clinical implications of comfort, thermal, skin, psychologic, and workplace effects.

Filtering facepiece respirators (FFR's) such as N95s have become widely used in appropriate settings for personal respiratory protection and are increasingly used beyond workplace settings. Concerns about possible adverse effects have appeared in many publications, particularly since the COVID-19 pandemic led to much more widespread use. This paper synthesizes known effects based upon review of publications in PubMed since 1995, addressing effects other than pulmonary and cardiovascular (reviewed elsewhere). Findings: (1) Subjective discomfort is very frequently reported; this includes general discomfort or organ-system-specific complaints such as respiratory, headache, dermatologic, and heat. Research methods are widely divergent, and we propose a taxonomy to classify such studies by methodology, study population (subjects, experimental vs. observational methodology, comparator, specificity, and timeframe) to facilitate synthesis. (2) Objective measures of increased heat and humidity within the mask are well documented. (3) Frequency and characteristics of dermatologic effects have been insufficiently evaluated. (4) Physical mask designs are varied, making generalizations challenging. (5) More studies of impact on work performance and communication are needed. (6) Studies of effect of FFR design and accompanying training materials on ease and consistency of use are needed.

Health effects of filtering facepiece respirators: Systematic review of pulmonary and cardiovascular effects.

Filtering facepiece respirators (FFRs) were introduced to protect the wearer by removing small particles from inspired air. FFRs are now also used to reduce the spread of transmissible agents from the wearer and are worn outside traditional healthcare and other workplaces. The COVID-19 pandemic increased concerns about potential adverse effects on wearers. A PUBMED query retrieved articles through June 2022. Abstracts and selected full-text articles were systematically reviewed by the authors. This article focuses upon cardiopulmonary physiologic effects (e.g., ventilation, CO2 elimination, oxygen uptake, and respiratory control) with emphasis upon current and potential research methods as well as summarizing results. 1985 records were identified, of which only 26% were published before 2020. FFR effects on CO2 elimination appear more likely to be significant than effects on oxygenation or cardiovascular function. While FFRs appear well tolerated by healthy persons, more research is needed for those with pulmonary or cardiac disorders, and for children. Many traditional pulmonary exercise study methods require special care when applied to filtering facepiece respirators. Studying additional parameters may explain the paradox of many subjective discomfort reports despite very limited physiologic effects.

Acute Changes in Ambient Temperature Are Associated With Adverse Changes in Cardiac Rhythm.

BACKGROUND: Both increases and decreases in ambient temperature have been associated with increased cardiovascular mortality and morbidity. However, the mechanism(s) remain unclear. OBJECTIVES: We examined associations between biomarkers of pathways thought to, in part, explain these associations and changes in ambient temperature in a panel of predominantly post-myocardial infarction or post-stent patients. METHODS: We studied 76 subjects who had a recent coronary event and were participating in a cardiac rehabilitation program. In these patients, we measured heart rate variability, repolarization, and baroreflex sensitivity parameters using Holter ECG recordings before and during supervised, graded, twice weekly, exercise sessions. Hourly temperature measurements were made at a monitoring site near the rehabilitation center. RESULTS: Using linear mixed models, we observed decreases in rMSSD (square root of the mean of the sum of the squared differences between adjacent NN intervals) and deceleration capacity, associated with increases in ambient temperature in the previous four days. Additionally, decreased rMSSD was associated with both increasing temperature (mean in previous 6 hours) in the summer and decreasing temperature (mean in the previous 3 weeks) in the winter. CONCLUSIONS: In a panel of cardiac rehabilitation patients, changes in ambient temperature were associated with decreases in markers of heart rate variability and baroreflex sensitivity, which may lead to increased risk of arrhythmic events and sudden death in post-infarction patients.

A role for transcription factor GTF2IRD2 in executive function in Williams-Beuren syndrome.

Executive functions are amongst the most heritable cognitive traits with twin studies indicating a strong genetic origin. However genes associated with this domain are unknown. Our research into the neurodevelopmental disorder Williams-Beuren syndrome (WBS) has identified a gene within the causative recurrent 1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be involved in executive functioning. Comparative genome array screening of 55 WBS patients revealed a larger ∼1.8 Mb microdeletion in 18% of cases, which results in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A multi-level analysis of cognitive, behavioural and psychological functioning in WBS patients showed that those with slightly larger deletions encompassing GTF2IRD2 were significantly more cognitively impaired in the areas of spatial functioning, social reasoning, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher-level (executive functioning) abilities and highlight the importance of integrating detailed molecular characterisation of patients with comprehensive neuropsychological profiling to uncover additional genotype-phenotype correlations. The identification of specific genes which contribute to executive function has important neuropsychological implications in the treatment of patients with conditions like WBS, and will allow further studies into their mechanism of action.

Are ambient ultrafine, accumulation mode, and fine particles associated with adverse cardiac responses in patients undergoing cardiac rehabilitation?

BACKGROUND: Mechanisms underlying previously reported air pollution and cardiovascular (CV) morbidity associations remain poorly understood. OBJECTIVES: We examined associations between markers of pathways thought to underlie these air pollution and CV associations and ambient particle concentrations in postinfarction patients. METHODS: We studied 76 patients, from June 2006 to November 2009, who participated in a 10-week cardiac rehabilitation program following a recent (within 3 months) myocardial infarction or unstable angina. Ambient ultrafine particle (UFP; 10-100 nm), accumulation mode particle (AMP; 100-500 nm), and fine particle concentrations (PM2.5; ≤ 2.5 µm in aerodynamic diameter) were monitored continuously. Continuous Holter electrocardiogram (ECG) recordings were made before and during supervised, graded, twice weekly, exercise sessions. A venous blood sample was collected and blood pressure was measured before sessions. RESULTS: Using mixed effects models, we observed adverse changes in rMSSD [square root of the mean of the sum of the squared differences between adjacent normal-to-normal (NN) intervals], SDNN (standard deviation of all NN beat intervals), TpTe (time from peak to end of T-wave), heart rate turbulence, systolic and diastolic blood pressures, C-reactive protein, and fibrinogen associated with interquartile range increases in UFP, AMP, and PM2.5 at 1 or more lag times within the previous 5 days. Exposures were not associated with MeanNN, heart-rate-corrected QT interval duration (QTc), deceleration capacity, and white blood cell count was not associated with UFP, AMP, and PM2.5 at any lag time. CONCLUSIONS: In cardiac rehabilitation patients, particles were associated with subclinical decreases in parasympathetic modulation, prolongation of late repolarization duration, increased blood pressure, and systemic inflammation. It is possible that such changes could increase the risk of CV events in this susceptible population.

Serum carotenoid concentrations predict lung function evolution in young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: A higher dietary intake of carotenoid-rich foods and higher circulating concentrations of carotenoids have been associated with better lung function in cross-sectional studies; however, the longitudinal association between carotenoids and lung function has shown conflicting results. OBJECTIVE: We examined the longitudinal association between serum carotenoids (ß-cryptoxanthin, α-carotene, ß-carotene, lutein/zeaxanthin, and lycopene) and the evolution of lung function. DESIGN: We evaluated our hypothesis in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. Spirometry testing was conducted at year 0 (1985-1986) and at follow-up in years 2, 5, 10, and 20; serum carotenoids were assayed at years 0 and 15, and diet was assessed at years 0 and 20. RESULTS: Year 0 sum of provitamin A carotenoids and ß-cryptoxanthin concentrations were associated with maximum forced vital capacity (FVC) (P ≤ 0.01) and forced expiratory volume in 1 s (FEV(1)) (P ≤ 0.05) (maximum across years 0-10) in linear regression models adjusted for age, race, height, study center, amount of physical activity, smoking status, and BMI. Year 0 lutein/zeaxanthin and lycopene were not associated with maximum lung function. Baseline concentrations of lutein/zeaxanthin, lycopene, sum of the 3 provitamin A carotenoids, ß-carotene, and ß-cryptoxanthin were each inversely associated with a decline from maximum FVC and FEV(1) (P ≤ 0.04). The sum of provitamin A carotenoids and lycopene remained significant after adjustment for dietary intake related to serum carotenoids (P ≤ 0.03). The 15-y change in provitamin A carotenoid and lutein/zeaxanthin concentrations was associated with a slower decline from maximum FVC and FEV(1) (P ≤ 0.04). CONCLUSION: These findings support an association between serum carotenoid concentrations and a decline in lung function.

Shock, adjust, decide: reproductive decision making in cystic fibrosis (CF) carrier couples--a qualitative study.

Cystic fibrosis (CF) is the most common recessive condition affecting the White British population. Facilitating reproductive decision making for couples at genetic risk for CF is an important aspect of genetic counseling practice in the UK. The purpose of this study was to explore the reproductive decision making process for 31 members of CF carrier couples (15 men and 16 women) with or without an affected child. The design involved a qualitative approach consisting of semi-structured interviews and data analysis informed by grounded theory methodology. Sex and personal experience of CF were identified as factors that may influence reproductive decision making. Findings suggest these hypotheses: (1) CF carrier couples who have an affected child/pregnancy, are more likely to embark on another pregnancy than couples who have a healthy child from an at-risk pregnancy, and (2) men and women play different roles in the reproductive decision making process. Data analysis resulted in development of a structured framework modeling the reproductive decision making process, which may be helpful in guiding genetic counseling with CF carrier couples and other at risk couples making reproductive decisions.

Household airborne Penicillium associated with peak expiratory flow variability in asthmatic children.

BACKGROUND: Exposure to airborne fungi has been associated with increased airway hyperreactivity and asthma prevalence. OBJECTIVE: To investigate the association between common indoor fungi and airway hyperreactivity measured by peak expiratory flow variability in asthmatic children. METHODS: Children 6 to 12 years of age (n = 225) with a physician diagnosis of asthma were enrolled in the study to have their peak expiratory flow recorded twice daily during a 2-week period. Genus-specific, quantitative, in-home airborne mold concentrations were measured. Logistic regression models were used to examine the relationship between a mean peak expiratory flow variability greater than 18.5% (75th percentile) and any mold in the home (total mold, Cladosporium, Penicillium, Aspergillus, and Alternaria). RESULTS: Mold was detected in 93% of the homes. The most common molds were Cladosporium in 72% and Penicillium in 42% of the samples. Controlling for sex, ethnicity, age, and winter season of sampling, Penicillium measured in the home was associated with a mean peak expiratory flow variability greater than 18.5% (odds ratio, 2.4; 95% confidence interval, 1.2-4.8). Greater peak expiratory flow variability was not associated with total mold or other mold measured in the home. CONCLUSION: Exposure to airborne Penicillium is associated with increased peak expiratory flow variability in asthmatic children.

Obesity-asthma association: is it explained by systemic oxidant stress?

BACKGROUND: The mechanism for the obesity-asthma association is unknown. This study evaluated the hypothesis that systemic oxidant stress explains this association. METHODS: This cross-sectional study used year-20 follow-up evaluation data of 2,865 eligible participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Current asthma was self-reported. Oxidant stress primarily was assessed by plasma F2-isoprostane concentrations. Obesity measures included categories of BMI and dual-energy x-ray absorptiometry-assessed fat mass index (FMI) and lean mass index (LMI). Logistic and linear regressions were used for analyses. RESULTS: Asthma was associated with higher plasma F2-isoprostane concentrations (p = 0.049); however, this association was not significant when adjusted for either gender or BMI. The BMI-asthma association was seen only among women (p = 0.03; gender-specific interaction, p = 0.01), and this association was not explained by plasma F2-isoprostane levels. Similarly, both FMI and LMI were positively associated with asthma in women (p = 0.20 and 0.01, respectively). These associations also were not explained by plasma F2-isoprostane levels. Similar results were obtained when plasma levels of oxidized low-density lipoprotein were used instead of F2-isoprostane levels to study the BMI-asthma association at the year-15 evaluation. CONCLUSIONS: Systemic oxidant stress, primarily assessed by plasma F2-isoprostane concentrations, was not independently associated with asthma and, therefore, may not explain the obesity-asthma association in women. The asthma-oxidant stress association is confounded by gender and obesity. This study is limited by the inability to measure airway oxidant stress. It is possible that another (as yet undetermined) measure of systemic oxidant stress may be more relevant in asthma.

Association of pediatric asthma severity with exposure to common household dust allergens.

BACKGROUND: Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma. OBJECTIVE: To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children. METHODS: Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education. RESULTS: Der p 1 house dust mite allergen concentration of 2.0 microg/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 microg/g and OR 2.55 95% CI 1.13, 5.73 for 10.0 microg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22). CONCLUSION: Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.

Increased cardiovascular risk associated with reduced kidney function.

BACKGROUND: Individuals with chronic kidney disease (CKD) are at substantial risk for cardiovascular mortality, but the risk associated with specific glomerular filtration rates (GFRs) is unknown. The objective of this study was to investigate the relationship between level of kidney function and the risk of cardiovascular mortality in a diverse population. METHODS AND RESULTS: This was a nonconcurrent cohort study of 34,982 ambulatory patients. Kidney function was entered into the model as a time-dependent variable to minimize misclassification and allow for improved estimate of the effect of decreasing GFR on cardiovascular mortality. The adjusted hazard ratio for cardiovascular mortality was 1.00 (95% CI 0.93-1.06) with an estimated GFR (eGFR) of 45-59; 1.77 (95% CI 1.65-1.89) with an eGFR 30-44; 3.75 (95% CI 3.47-4.06) with an eGFR 15-29, and 3.83 (95% CI 3.40-4.33) with an eGFR <15. CONCLUSION: We demonstrate a graded risk of cardiovascular mortality with decreasing GFR, with a marked increase with an eGFR <45 ml/min/1.73 m(2). These data also suggest that the availability of eGFR to physicians has had little impact on reducing the cardiovascular risk facing individuals with CKD. Our findings further highlight the public health significance of CKD and the importance of its early identification and management to reduce cardiovascular mortality.

Diagnosis and management of work-related asthma: American College Of Chest Physicians Consensus Statement.

BACKGROUND: A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). METHODS: A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. RESULTS: The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. CONCLUSIONS: The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.

Primary prevention of occupational asthma: identifying and controlling exposures to asthma-causing agents.

BACKGROUND: Primary prevention of occupational asthma requires timely identification and regulation of asthma-causing agents. METHODS: We examined 39 substances identified as causing allergic occupational asthma in the US to determine the basis for their identification and their regulatory status. We compared them with occupational asthmagens identified and regulated in the UK and Germany. RESULTS: US regulatory agencies have not established consistent, evidence-based methods to identify and control exposures to substances that cause occupational asthma. Occupational asthmagens are identified primarily by non-regulatory US organizations, and most are not regulated to prevent asthma. CONCLUSIONS: Implementing an evidence-based identification and regulatory process for occupational asthmagens will help to ensure primary prevention of occupational asthma in the US. This should include: establishing consistent identification criteria; publishing a list of occupational asthmagens; collecting use, exposure, and health effects information on asthma-causing substances; requiring medical surveillance and medical removal protection in addition to exposure limits; and stimulating development of safer alternatives.

Trimerization of collagen IX alpha-chains does not require the presence of the COL1 and NC1 domains.

Collagen IX is a heterotrimer of three alpha-chains, which consists of three COL domains (collagenous domains) (COL1-COL3) and four NC domains (non-collagenous domains) (NC1-NC4), numbered from the C-terminus. Although collagen IX chains have been shown to associate via their C-terminal NC1 domains and form a triple helix starting from the COL1 domain, it is not known whether chain association can occur at other sites and whether other collagenous and non-collagenous regions are involved. To address this question, we prepared five constructs, two long variants (beginning at the NC4 domain) and three short variants (beginning at the COL2 domain), all ending at the NC2 domain (or NC2 replaced by NC1), to study association and selection of collagen IX alpha-chains. Both long variants were able to associate with NC1 or NC2 at the C-terminus and form various disulfide-bonded trimers, but the specificity of chain selection was diminished compared with full-length chains. Trimers of the long variant ending at NC2 were shown to be triple helical by CD. Short variants were not able to assemble into disulfide-bonded trimers even in the presence of both conserved cysteine residues from the COL1-NC1 junction. Our results demonstrate that collagen IX alpha-chains can associate in the absence of COL1 and NC1 domains to form a triple helix, but the COL2-NC2 region alone is not sufficient for trimerization. The results suggest that folding of collagen IX is a co-operative process involving multiple COL and NC domains and that the COL1-NC1 region is important for chain specificity.

Asbestos-related lung disease.

The inhalation of asbestos fibers may lead to a number of respiratory diseases, including lung cancer, asbestosis, pleural plaques, benign pleural effusion, and malignant mesothelioma. Although exposure is now regulated, patients continue to present with these diseases because of the long latent period between exposure and clinical disease. Presenting signs and symptoms tend to be nonspecific; thus, the occupational history helps guide clinical suspicion. High-risk populations include persons in construction trades, boilermakers, shipyard workers, railroad workers, and U.S. Navy veterans. Every effort should be made to minimize ongoing exposure. Patients with a history of significant asbestos exposure may warrant diagnostic testing and follow-up assessment, although it is unclear whether this improves outcomes. Patients with significant exposure and dyspnea should have chest radiography and spirometry. The prognosis depends on the specific disease entity. Asbestosis generally progresses slowly, whereas malignant mesothelioma has an extremely poor prognosis. The treatment of patients with asbestos exposure and lung cancer is identical to that of any patient with lung cancer. Because exposure to cigarette smoke increases the risk of developing lung cancer in patients with a history of asbestos exposure, smoking cessation is essential. Patients with asbestosis or lung cancer should receive influenza and pneumococcal vaccinations.

Implications for occupational exposure to particulate matter.

The demonstrated effects of lower levels of ambient particles on cardiovascular and respiratory system morbidity and mortality were initially surprising in light of current concepts of occupational particle exposure and acute and chronic cardiopulmonary effects. Specifically, the exposure levels, as defined by the weight of the particles per liter of breathing air, at which recognized disease occurs under workplace conditions are considerably higher than the observed levels of ambient particles associated with serious adverse health effects. The possible reasons for this difference have not been adequately addressed. To further address this question, a re-examination of workplace exposure-response relationships is needed, which may include emphasis on measuring exposures to fine and ultrafine particles rather than to total particle mass concentration alone.

Low-level ozone exposure and respiratory symptoms in infants.

OBJECTIVE: Recent studies indicate that the U.S. Environmental Protection Agency (EPA) ozone standards may not protect sensitive individuals. In this study we examined respiratory effects of ozone in infants who may be vulnerable, particularly if they are children of asthmatic mothers. DESIGN: Women delivering babies at one of five hospitals in southwestern Virginia between 1994 and 1996 were invited to participate in a cohort study; 780 women enrolled. Ambient air quality data (ozone and particulate matter) were collected at a central monitoring site. PARTICIPANTS: This analysis is of 691 infants followed for approximately 83 days between 10 June and 31 August 1995 and/or 1996 ; they contributed a total of 52,421 infant-days of follow-up. Mothers were interviewed at enrollment and approximately biweekly to report infants' daily symptoms. Repeated measures logistic regression models were run separately for wheeze, difficulty breathing, and cough. Ozone metrics included 24-hr average, peak 1-hr, and maximum 8-hr average. Analyses were repeated for the 61 infants whose mothers had asthma. RESULTS: For every interquartile-range increase in same-day 24-hr average ozone, likelihood of wheeze increased 37% [95% confidence interval (CI), 2-84%]. Among infants of asthmatic mothers, same-day 24-hr average ozone increased likelihood of wheeze 59% (95% CI, 1-154%) and of difficulty breathing 83% (95% CI, 42-136%). Maximum 8-hr ozone and peak 1-hr ozone were associated with difficulty breathing, but not wheeze, in infants of asthmatic mothers. Ozone was not associated with cough. CONCLUSIONS: At levels of ozone exposure near or below current U.S. EPA standards, infants are at increased risk of respiratory symptoms, particularly infants whose mothers have physician-diagnosed asthma.