Recurrent Pneumothorax with CPAP Therapy for Obstructive Sleep Apnea.

Pulmonary barotrauma such as pneumothorax (PTX) is a known complication of invasive mechanical ventilation. However, it is uncommonly reported with the use of noninvasive positive pressure ventilation (NPPV) and CPAP (continuous positive airway pressure) therapy. We present a case of a 66-year-old female who presented with chronic dyspnea on exertion secondary to right-sided diaphragmatic hernia. The patient also underwent a home sleep study which suggested obstructive sleep apnea (OSA) for which she was initiated on CPAP. She then underwent surgical repair of her right diaphragmatic hernia. The patient developed pneumothorax three times over the course of the following several months, once on the right side and twice on the left side. The patient's incidences of PTX had a temporal association with the CPAP initiation. Her CPAP therapy was discontinued permanently after the third occurrence of PTX. With this case report, we highlight the risk of barotrauma with the use of CPAP for OSA. There are very few reported cases of PTX in association with NPPV therapy for OSA. The lung-protective ventilation strategies and limiting the positive airway pressures can help reduce the risk of pulmonary barotrauma with CPAP.

Authors' response to comments from Nachman KE et al.

Authors' response to comments letter to the editor from Nachman KE et al.

Updated systematic review: associations between proximity to animal feeding operations and health of individuals in nearby communities.

OBJECTIVE: The objective of this review was to update a systematic review of associations between living near an animal feeding operation (AFO) and human health. METHODS: The MEDLINE® and MEDLINE® In-Process, Centre for Agricultural Biosciences Abstracts, and Science Citation Index databases were searched. Reference lists of included articles were hand-searched. Eligible studies reported exposure to an AFO and an individual-level human health outcome. Two reviewers performed study selection and data extraction. RESULTS: The search returned 3702 citations. Sixteen articles consisting of 10 study populations were included in the analysis. The health outcomes were lower and upper respiratory tracts, MRSA, other infectious disease, neurological, psychological, dermatological, otologic, ocular, gastrointestinal, stress and mood, and other non-infectious health outcomes. Most studies were observational and used prevalence measures of outcome. An association between Q fever risk and proximity to goat production was reported. Other associations were unclear. Risk of bias was serious or critical for most exposure-outcome associations. Multiplicity (i.e., a large number of potentially correlated outcomes and exposures assessed on the same study subjects) was common in the evidence base. CONCLUSIONS: Few studies reported an association between surrogate clinical outcomes and AFO proximity for respiratory tract-related outcomes. There were no consistent dose-response relationships between surrogate clinical outcome and AFO proximity. A new finding was that Q fever in goats is likely associated with an increased Q fever risk in community members. The review results for the non-respiratory health outcomes were inconclusive because only a small number of studies were available or the between-study results were inconsistent. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010521.

The association between proximity to animal-feeding operations and community health: a protocol for updating a systematic review.

BACKGROUND: Livestock and poultry operations that feed large numbers of animals are common. Facility capacity varies, but it is not uncommon for facilities to house 1,000 swine with multiple barns at a single site, feedlots to house 50,000 cattle, and poultry houses to house 250,000 hens. There is primary research that suggests livestock facilities that confine animals indoors for feeding can represent a health hazard for surrounding communities. In this protocol, we describe a review about the association between proximity to animal-feeding operations (AFOs) and the health of individuals in nearby communities. A systematic review of the topic was published by some members of our group in 2010. The purpose of this review is to update that review. METHODS/DESIGN: The populations of interest are people living in communities near livestock production facilities. Outcomes of interest are any health outcome measured in humans such as respiratory disease, gastrointestinal disease, and mental health. Measures of antibiotic resistance in people from the communities compared to measures of resistance found in animals and the environment on animal-feeding operations will also be summarized. The exposure of interest will be exposure to livestock production using a variety of metrics such as distance from facilities, endotoxin levels, and measures of odor. Electronic searches will be conducted using MEDLINE and MEDLINE In-Process (via OvidSP), CAB Abstracts (via Web of Knowledge), and Science Citation Index (via Web of Knowledge). No language or date restriction will be applied. We will access the risk of bias using a pilot version of a tool developed by the Methods Groups of the Cochrane Collaboration for non-randomized interventions.We propose to conduct a meta-analysis for each health metric (e.g., combining all respiratory disease outcomes, combining all gastrointestinal outcomes). A planned subgroup analysis will be based on the domains of the risk of bias. DISCUSSION: This systematic review will provide synthesis of current evidence reporting the association between living near an animal-feeding operation and human health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014010521.

Official American Thoracic Society technical standards: spirometry in the occupational setting.

PURPOSE: This document addresses aspects of the performance and interpretation of spirometry that are particularly important in the workplace, where inhalation exposures can affect lung function and cause or exacerbate lung diseases, such as asthma, chronic obstructive pulmonary disease, or fibrosis. METHODS: Issues that previous American Thoracic Society spirometry statements did not adequately address with respect to the workplace were identified for systematic review. Medline 1950-2012 and Embase 1980-2012 were searched for evidence related to the following: training for spirometry technicians; testing posture; appropriate reference values to use for Asians in North America; and interpretative strategies for analyzing longitudinal change in lung function. The evidence was reviewed and technical recommendations were developed. RESULTS: Spirometry performed in the work setting should be part of a comprehensive workplace respiratory health program. Effective technician training and feedback can improve the quality of spirometry testing. Posture-related changes in FEV1 and FVC, although small, may impact interpretation, so testing posture should be kept consistent and documented on repeat testing. Until North American Asian-specific equations are developed, applying a correction factor of 0.88 to white reference values is considered reasonable when testing Asian American individuals in North America. Current spirometry should be compared with previous tests. Excessive loss in FEV1 over time should be evaluated using either a percentage decline (15% plus loss expected due to aging) or one of the other approaches discussed, taking into consideration testing variability, worker exposures, symptoms, and other clinical information. CONCLUSIONS: Important aspects of workplace spirometry are discussed and recommendations are provided for the performance and interpretation of workplace spirometry.

Chronic obstructive pulmonary disease patients have greater systemic responsiveness to ex vivo stimulation with swine dust extract and its components versus healthy volunteers.

Chronic obstructive pulmonary disease (COPD) is characterized by an airway and systemic inflammatory response. Bioaerosols/organic dusts are important agricultural pollutants that may lead to COPD. These environments are complex, containing a rich source of various microbial components. The objective of this study was to determine whether individuals with COPD have enhanced systemic responsiveness to settled swine facility organic dust extract (ODE) or its main pathogenic components (peptidoglycan [PGN], lipopolysaccharide [LPS]) versus healthy volunteers. A modified whole blood assay (WBA) that included occupational levels of ODE and concentrations of LPS and PGN found in ODE was used to determine systemic responsiveness (mediator release), and sputum inflammatory markers were measured to explore for systemic and airway associations. Sputum samples were evaluated for cell counts, and tumor necrosis factor (TNF)-α, interleukin (IL)-8/CXCL8, IL-6, and IL-10. Ex vivo whole blood stimulation with ODE, LPS, and PGN each resulted in significant mediator release in all subjects, with the highest occurring with ODE; PGN resulted in significantly enhanced TNF-α and IL-8 as compared to LPS. COPD subjects demonstrated greater systemic responsiveness using the modified WBA versus healthy controls. Within COPD subjects, blood baseline TNF-α, IL-8, and IL-10 and ODE-, PGN-, and LPS-stimulated IL-8 levels significantly correlated with lung function. In conclusion, dust-induced mediator release was robust, and PGN, in part, resembled dust-induced mediator release. Subjects with COPD demonstrated increased mediator release following ex vivo whole blood stimulation with bioaerosol components, suggesting that circulating blood cells in COPD subjects may be primed to respond greater to microbial/inflammatory insult.

Pulmonary function reductions among potentially susceptible subgroups of agricultural workers in Colorado and Nebraska.

OBJECTIVE: Organic dust inhalation has been associated with adverse respiratory responses among agricultural workers. We evaluated factors that may confer increased susceptibility to these health effects. METHODS: We quantified personal work shift exposures to inhalable dust, endotoxin, and its 3-hydroxy fatty acid constituents, and evaluated changes in pulmonary function among 137 grain elevator, cattle feedlot, dairy, and corn farm workers. RESULTS: Increased dust exposure was associated with work shift reductions in lung function. Although interpretation is limited because of small samples, a suggestion of stronger exposure-response relationships was observed among smokers, as well as workers reporting pesticide/herbicide application, asthma, or allergies, and those with genetic polymorphisms (TLR4) (Pinteraction ≤ 0.05). CONCLUSIONS: A better understanding of factors leading to increased susceptibility of adverse respiratory outcomes is needed to optimize exposure reduction strategies and develop more comprehensive wellness programs.

Respiratory issues in beef and pork production: recommendations from an expert panel.

This paper summarizes "Respiratory Issues in Confined Feeding Operations," a panel discussion at the Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, "Be Safe, Be Profitable: Protecting Workers in Agriculture," Dallas/Fort Worth, Texas, January 27-28, 2010. Occupational exposure to confined animal feeding operations is associated with cough, wheezing, and shortness of breath. Published data shows that 20% to 40% of hog confinement workers experience such symptoms, although most are able to continue working in this industry. Endotoxin is one component of hog barn dust that is associated with respiratory disease in workers. Endotoxin levels on cattle feedlots can also be in the range linked with occupational lung disease. The cattle industry has not yet prepared guidance documents for producers, in part because much less is known about the prevalence of lung disease in its workers. However, the pork industry provides information for pork producers on reducing their respiratory health risks through a multifaceted approach, including the use of respirators. Some jobs cannot be done safely without respiratory protection, such as entering manure pits. It is less clear for other jobs when respirators should be worn. Use of respiratory protection should be considered but not mandated for all persons working in close proximity to livestock in dusty conditions. A respiratory protection program may also serve as a cost effective biosecurity measure to protect animals from human pathogens such as influenza virus. Proper design and management of barn ventilation systems is critical for maintaining temperature and humidity levels for optimal animal growth; as well as decreasing the level of gases and respirable dusts. The pork and the cattle industries support occupational health and safety; however, the governmental guidance and recommendations for such programs are limited for the agricultural industries as a whole. The industries should lead the way in the effort to improve respiratory protection for workers. Overall, a team approach that includes input from managers, workers, and veterinarians is important for the reduction of respiratory hazards on livestock farms.

The association between proximity to animal feeding operations and community health: a systematic review.

BACKGROUND: A systematic review was conducted for the association between animal feeding operations (AFOs) and the health of individuals living near AFOs. METHODOLOGY/PRINCIPAL FINDINGS: The review was restricted to studies reporting respiratory, gastrointestinal and mental health outcomes in individuals living near AFOs in North America, European Union, United Kingdom, and Scandinavia. From June to September 2008 searches were conducted in PUBMED, CAB, Web-of-Science, and Agricola with no restrictions. Hand searching of narrative reviews was also used. Two reviewers independently evaluated the role of chance, confounding, information, selection and analytic bias on the study outcome. Nine relevant studies were identified. The studies were heterogeneous with respect to outcomes and exposures assessed. Few studies reported an association between surrogate clinical outcomes and AFO proximity. A negative association was reported when odor was the measure of exposure to AFOs and self-reported disease, the measure of outcome. There was evidence of an association between self-reported disease and proximity to AFO in individuals annoyed by AFO odor. CONCLUSIONS/SIGNIFICANCE: There was inconsistent evidence of a weak association between self-reported disease in people with allergies or familial history of allergies. No consistent dose response relationship between exposure and disease was observable.

Endotoxin exposure and inflammation markers among agricultural workers in Colorado and Nebraska.

The adverse respiratory effects of agricultural dust inhalation are mediated in part by endotoxin, a constituent of gram-negative bacterial cell walls. This study quantified personal work-shift exposures to inhalable dust, endotoxin, and its reactive 3-hydroxy fatty acid (3-OHFA) constituents among workers in grain elevators, cattle feedlots, dairies, and on corn farms. Exposures were compared with post-work-shift nasal lavage fluid inflammation markers and respiratory symptoms. Breathing-zone personal air monitoring was performed over one work shift to quantify inhalable dust (Institute of Medicine samplers), endotoxin (recombinant factor C [rFC] assay), and 3-OHFA (gas chromatography/mass spectrometry). Post-shift nasal lavage fluids were assayed for polymorphonuclear neutrophils (PMN), myeloperoxidase (MPO), interleukin 8 (IL-8), albumin, and eosinophilic cation protein (ECP) concentrations. The geometric mean (GSD) of endotoxin exposure (rFC assay) among the 125 male participants was 888 +/- (6.5) EU/m(3), and 93% exceeded the proposed exposure limit (50 EU/m(3)). Mean PMN, MPO, albumin, and ECP levels were two- to threefold higher among workers in the upper quartile of 3-OHFA exposure compared to the lowest exposure quartile. Even numbered 3-OHFA were most strongly associated with nasal inflammation. Symptom prevalence was not elevated among exposed workers, possibly due to endotoxin tolerance or a healthy worker effect in this population. This is the first study to evaluate the relationship between endotoxin's 3-OHFA constituents in agricultural dust and nasal airway inflammation. More research is needed to characterize the extent to which these agents contribute to respiratory disease among agricultural workers.

One-year outcomes of a behavioral therapy intervention trial on sleep quality and cancer-related fatigue.

PURPOSE: To determine 1-year outcomes of a four-component behavioral therapy (BT) sleep intervention (Individualized Sleep Promotion Plan [ISPP]) versus a healthy eating control (HEC) on cancer-related fatigue in women receiving breast cancer adjuvant chemotherapy treatment (CTX). PATIENTS AND METHODS: A total of 219 participants from 12 oncology clinics were randomly assigned in a clinical trial. Before CTX, research nurses coached intervention participants to develop a BT plan including stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene. BT plans were revised before each CTX and 30, 60, and 90 days after the last CTX and reinforced 7 to 9 days later. HEC participants received nutritional information and equal attention. Pittsburgh Sleep Quality Index (PSQI), Daily Diary, Wrist Actigraph, and Piper Fatigue Scale measures and Repeated Linear Mixed Model analysis following the Intent to Treat paradigm were used. RESULTS: Sleep quality differed over 1 years time (F [4,162] = 7.7, P < .001; by group, F [1,173] = 4.8, P = .029; and over time by group, F [4,162] = 3.3, P = .013). Pairwise comparisons revealed significant differences between groups at 90 days (P = .002) but not at 1 year (P = .052). Seven days of diary and actigraphy data did not corroborate with monthly reflections (PSQI). The night awakenings (Actigraph) pattern was significantly different by group over time (P = .046), with no differences between groups at 90 days or at 1 year. Fatigue was lower at 1 year than before CTX; no group effects were found. CONCLUSION: The BT group, on average, experienced significant improvement on global sleep quality compared with the HEC group, but not on objective sleep or fatigue outcomes.

Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice.

Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in increased bronchoalveolar lavage fluid neutrophils and macrophages after single and repetitive exposures. Lavage fluid TNFalpha, IL-6, keratinocyte chemoattractant, and macrophage inflammatory protein-2 were significantly increased after single and repetitive dust exposures, but were dampened in 2-wk dust-exposed mice compared with single exposure. Dust exposure induced PKCalpha and -epsilon activation in isolated tracheal epithelial cells but were dampened with repetitive exposures. Ex vivo stimulation of alveolar macrophages from 2-wk animals demonstrated reduced cytokine responsiveness and phagocytic ability. Significant lung pathology occurred with development of mixed mononuclear cellular aggregates (T and B lymphocytes, phagocytes) after repetitive dust exposure, a novel observation. Airway hyperresponsiveness to methacholine occurred after single dust exposure but resolved after 2 wk. Collectively, intranasal exposure to DE results in significant lung inflammatory and pathological responses marked by a modulated innate immune response to single and repetitive dust exposures that is associated with PKC activity.

Behavioral therapy intervention trial to improve sleep quality and cancer-related fatigue.

BACKGROUND: To determine whether sleep quality and fatigue associated with breast cancer adjuvant chemotherapy treatments can be improved with behavioral therapy (BT) [Individualized Sleep Promotion Plan (ISPP)] including modified stimulus control, modified sleep restriction, relaxation therapy, and sleep hygiene. METHODS: Randomized-controlled trial based on Piper Integrated Fatigue Model, 219 stages I-IIIA breast cancer patients. Prior to the initial chemotherapy treatment, BT participants developed an ISPP plan that was regularly reinforced and revised. Controls received healthy eating information and attention. Pittsburgh Sleep Quality Index (PSQI), daily diary, actigraph, and Piper Fatigue Scale (PFS) data were collected 2 days prior, during the 7 days after each treatment, and 30 days after the last treatment. Repeated measures analysis of variance was used. RESULTS: Prior to chemotherapy, participants reported mild fatigue and fairly poor sleep quality. All variables changed over time. A group by time interaction was found for sleep quality (PSQI) improving in the BT group. Diary revealed group differences on number of awakenings, minutes awake after sleep onset, and sleep efficiency. Fatigue (PFS) was similar between groups. CONCLUSIONS: The BT group showed improved sleep quality over time and better sleep (diary). Perceptions of improved sleep quality over time are not consistently associated with diary or actigraph, or result in lower fatigue.

Repetitive organic dust exposure in vitro impairs macrophage differentiation and function.

BACKGROUND: Organic dust exposure in the agricultural industry results in significant airway disease and lung function decrease. Mononuclear phagocytes are key cells that mediate the inflammatory and innate immune response after dust exposure. OBJECTIVE: We sought to investigate the effect of organic dust extract (ODE) from modern swine operations on monocyte-derived macrophage (MDM) phenotype and function. METHODS: Peripheral blood monocytes were obtained by means of elutriation methodology (>99% CD14(+)) and differentiated into macrophages in the presence of GM-CSF (1 week) with and without ODE (0.1%). At 1 week, cells were analyzed by means of flow cytometry for cell-surface marker expression (HLA-DR, CD80, CD86, Toll-like receptor 2, Toll-like receptor 4, mCD14, and CD16), phagocytosis (IgG-opsonized zymosan particles), and intracellular killing of Streptococcus pneumoniae. At 1 week, MDMs were rechallenged with high-dose ODE (1%), LPS, and peptidoglycan (PGN), and cytokine levels (TNF-alpha, IL-6, IL-10, and CXCL8/IL-8) were measured. Comparisons were made to MDMs conditioned with heat-inactivated dust, endotoxin-depleted dust, LPS, and PGN to elucidate ODE-associated factors. RESULTS: Expression of HLA-DR, CD80, and CD86; phagocytosis; and intracellular bacterial killing were significantly decreased with ODE-challenged versus control MDMs. Responses were retained after marked depletion of endotoxin. PGN, LPS, and PGN plus LPS significantly reduced MDM surface marker expression and, except for LPS alone, also reduced phagocytosis. ODE-challenged MDMs had significantly diminished cytokine responses (TNF-alpha, IL-6, and IL-10) after repeat challenge with high-dose ODE. Cross-tolerant cytokine responses were also observed. CONCLUSION: Repetitive organic dust exposure significantly decreases markers of antigen presentation and host defense function in MDMs. Bacterial cell components appear to be driving these impaired responses.

Bronchodilator responsiveness in swine veterinarians.

OBJECTIVE: Swine veterinarians are known to be at risk for respiratory symptoms and airflow obstruction. The present study reassessed the prevalence of respiratory complaints and pulmonary function abnormalities in swine veterinarians and sought to characterize their response to bronchodilators. METHODS: A cross-sectional study was conducted during the American Association of Swine Veterinarians annual meeting. Subjects completed a respiratory symptom and workplace exposure history questionnaire and spirometry. Subjects with airflow obstruction were assessed for a post-bronchodilator response with beta2 agonist administration. RESULTS: Participants included 58 veterinarians (mean age, 45.5 years). Work-related symptoms assessed by questionnaire included rhinitis symptoms (60.3%), cough and chest tightness (55.2%), and wheezing (35.1%). Airflow obstruction was detected in 11/58 (19%) of subjects by spirometry. Only 2/9 (22.2%) met American Thoracic Society criteria for reversibility with bronchodilator administration. CONCLUSIONS: Respiratory symptoms and airway obstruction remain common findings in swine veterinarians. Airflow obstruction was not consistently reversible with beta agonists, suggesting that swine barn exposure may be a risk factor for irreversible airflow obstruction.

Hog barn dust slows airway epithelial cell migration in vitro through a PKCalpha-dependent mechanism.

Agricultural work and other occupational exposures are responsible for approximately 15% of chronic obstructive pulmonary disease (COPD). COPD involves airway remodeling in response to chronic lung inflammatory events and altered airway repair mechanisms. However, the effect of agricultural dust exposure on signaling pathways that regulate airway injury and repair has not been well characterized. A key step in this process is migration of airway cells to restore epithelial integrity. We have previously shown that agents that activate the critical regulatory enzyme protein kinase C (PKC) slow cell migration during wound repair. Based on this observation and direct kinase measurements that demonstrate that dust extract from hog confinement barns (HDE) specifically activates the PKC isoforms PKCalpha and PKCepsilon, we hypothesized that HDE would slow wound closure time in airway epithelial cells. We utilized the human bronchial epithelial cell line BEAS-2B and transfected BEAS-2B cell lines that express dominant negative (DN) forms of PKC isoforms to demonstrate that HDE slows wound closure in BEAS-2B and PKCepsilon DN cell lines. However, in PKCalpha DN cells, wound closure following HDE treatment is not significantly different than media-treated cells. These results suggest that the PKCalpha isoform is an important regulator of cell migration in response to agricultural dust exposure.

Feedlot dust stimulation of interleukin-6 and -8 requires protein kinase Cepsilon in human bronchial epithelial cells.

Individuals exposed to dusts from concentrated animal feeding operations report increased numbers of respiratory tract symptoms, and bronchoalveolar lavage samples from such individuals demonstrate elevated lung inflammatory mediators, including interleukin (IL)-8 and IL-6. We previously found that exposure of bronchial epithelial cells to hog barn dusts resulted in a protein kinase C (PKC)-dependent increase in IL-6 and IL-8 release. We hypothesized that cattle feedlot dusts would also generate bronchial epithelial interleukin release in vitro. To test this, we used interleukin ELISAs and direct PKC isoform assays. We found that a dust extract from cattle feedlots [feedlot dust extract (FLDE)] augments PKC activity of human bronchial epithelial cells in vitro. A 5-10% dilution of FLDE stimulated a significant release of IL-6 and IL-8 at 6-24 h in a PKC-dependent manner vs. control medium-treated cells. An increase in PKCalpha activity was observed with 1 h of FLDE treatment, and PKCepsilon activity was elevated at 6 h of FLDE exposure. The PKCalpha inhibitor, Gö-6976, did not inhibit FLDE-stimulated IL-8 and IL-6 release. However, the PKCepsilon inhibitor, Ro 31-8220, effectively inhibited FLDE-stimulated IL-8 and IL-6 release. Inhibition of FLDE-stimulated IL-6 and IL-8 was confirmed in a dominant-negative PKCepsilon-expressing BEAS-2B cell line but not observed in a PKCalpha dominant negative BEAS-2B cell line. These data support the hypothesis that FLDE exposure stimulates bronchial epithelial IL-8 and IL-6 release via a PKCepsilon-dependent pathway.