Role of Air Pollution in the Development of Asthma Among Children with a History of Bronchiolitis in Infancy.

BACKGROUND: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. METHODS: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. RESULTS: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. CONCLUSION: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis.

Air pollution after acute bronchiolitis is a risk factor for preschool asthma: a nested case-control study.

BACKGROUND: Acute bronchiolitis and air pollution are both risk factor of pediatric asthma. This study aimed to assess subsequent exposure to air pollutants related to the inception of preschool asthma in infants with acute bronchiolitis. This study aimed to assess subsequent exposure to air pollutants related to the inception of preschool asthma in infants with acute bronchiolitis. METHODS: A nested case-control retrospective study was performed at the Kaohsiung Medical University Hospital systems between 2009 and 2019. The average concentration of PM10, PM2.5, SO2, NO, NO2, and NOX was collected for three, six, and twelve months after the first infected episode. Adjusted regression models were employed to evaluate the association between asthma and air pollution exposure after bronchiolitis. RESULTS: Two thousand six hundred thirty-seven children with acute bronchiolitis were included. Exposure to PM10, PM2.5, SO2, NO, NO2, and NOX in the three, six, and twelve months following an episode of bronchiolitis was found to significantly increase the risk of preschool asthma in infants with a history of bronchiolitis.(OR, 95%CI: PM10 = 1.517-1.559, 1.354-1.744; PM2.5 = 2.510-2.603, 2.148-3.061; SO2 = 1.970-2.040, 1.724-2.342; ; NO = 1.915-1.950, 1.647-2.272; NO2 = 1.915-1.950, 1.647-2.272; NOX = 1.752-1.970, 1.508-2.252) In a sensitive analysis of hospitalized infants, only PM10, PM2.5, SO2, and NO were found to have significant effects during all time periods. (OR, 95%CI: PM10 = 1.613-1.650, 1.240-2.140; PM2.5 = 2.208-2.286, 1.568-3.061; SO2 = 1.679-1.622, 1.197-2.292; NO = 1.525-1.557, 1.094-2.181) CONCLUSION: The presence of ambient PM10, PM2.5, SO2 and NO in the three, six, and twelve months following an episode of acute bronchiolitis has been linked to the development of preschool asthma in infants with a history of acute bronchiolitis.

Increased risk of emergency department presentations for bronchiolitis in infants exposed to air pollution.

Air pollution has been linked to an increased risk of several respiratory diseases in children, especially respiratory tract infections. The present study aims to evaluate the association between pediatric emergency department (PED) presentations for bronchiolitis and air pollution. PED presentations due to bronchiolitis in children aged less than 1 year were retrospectively collected from 2007 to 2018 in Padova, Italy, together with daily environmental data. A conditional logistic regression based on a time-stratified case-crossover design was performed to evaluate the association between PED presentations and exposure to NO2 , PM2.5, and PM10. Models were adjusted for temperature, relative humidity, atmospheric pressure, and public holidays. Delayed effects in time were evaluated using distributed lag non-linear models. Odds ratio for lagged exposure from 0 to 14 days were obtained. Overall, 2251 children presented to the PED for bronchiolitis. Infants' exposure to higher concentrations of PM10 and PM2.5 in the 5 days before the presentation to the PED increased the risk of accessing the PED by more than 10%, whereas high concentrations of NO2 between 2 and 12 days before the PED presentation were associated with an increased risk of up to 30%. The association between pollutants and infants who required hospitalization was even greater. A cumulative effect of NO2 among the 2 weeks preceding the presentation was also observed. In summary, PM and NO2 concentrations are associated with PED presentations and hospitalizations for bronchiolitis. Exposure of infants to air pollution could damage the respiratory tract mucosa, facilitating viral infections and exacerbating symptoms.

Work-related adverse respiratory health outcomes at a machine manufacturing facility with a cluster of bronchiolitis, alveolar ductitis and emphysema (BADE).

OBJECTIVES: Four machine manufacturing facility workers had a novel occupational lung disease of uncertain aetiology characterised by lymphocytic bronchiolitis, alveolar ductitis and emphysema (BADE). We aimed to evaluate current workers' respiratory health in relation to job category and relative exposure to endotoxin, which is aerosolised from in-use metalworking fluid. METHODS: We offered a questionnaire and spirometry at baseline and 3.5 year follow-up. Endotoxin exposures were quantified for 16 production and non-production job groups. Forced expiratory volume in one second (FEV1) decline ≥10% was considered excessive. We examined SMRs compared with US adults, adjusted prevalence ratios (aPRs) for health outcomes by endotoxin exposure tertiles and predictors of excessive FEV1 decline. RESULTS: Among 388 (89%) baseline participants, SMRs were elevated for wheeze (2.5 (95% CI 2.1 to 3.0)), but not obstruction (0.5 (95% CI 0.3 to 1.1)). Mean endotoxin exposures (range: 0.09-28.4 EU/m3) were highest for machine shop jobs. Higher exposure was associated with exertional dyspnea (aPR=2.8 (95% CI 1.4 to 5.7)), but not lung function. Of 250 (64%) follow-up participants, 11 (4%) had excessive FEV1 decline (range: 403-2074 mL); 10 worked in production. Wheeze (aPR=3.6 (95% CI 1.1 to 12.1)) and medium (1.3-7.5 EU/m3) endotoxin exposure (aPR=10.5 (95% CI 1.3 to 83.1)) at baseline were associated with excessive decline. One production worker with excessive decline had BADE on subsequent lung biopsy. CONCLUSIONS: Lung function loss and BADE were associated with production work. Relationships with relative endotoxin exposure indicate work-related adverse respiratory health outcomes beyond the sentinel disease cluster, including an incident BADE case. Until causative factors and effective preventive strategies for BADE are determined, exposure minimisation and medical surveillance of affected workforces are recommended.

Immune Checkpoint Inhibitor Therapy-related Pneumonitis: Patterns and Management.

In recent years, the use of immune checkpoint inhibitor (ICI) therapy has rapidly grown, with increasing U.S. Food and Drug Administration approvals of a variety of agents used as first- and second-line treatments of various malignancies. ICIs act through a unique mechanism of action when compared with those of conventional chemotherapeutic agents. ICIs target the cell surface receptors cytotoxic T-lymphocyte antigen-4, programmed cell death protein 1, or programmed cell death ligand 1, which result in immune system-mediated destruction of tumor cells. Immune-related adverse events are an increasingly recognized set of complications of ICI therapy that may affect any organ system. ICI therapy-related pneumonitis is an uncommon but important complication of ICI therapy, with potential for significant morbidity and mortality. As the clinical manifestation is often nonspecific, CT plays an important role in diagnosis and triage. Several distinct radiographic patterns of pneumonitis have been observed: (a) organizing pneumonia, (b) nonspecific interstitial pneumonia, (c) hypersensitivity pneumonitis, (d) acute interstitial pneumonia-acute respiratory distress syndrome, (e) bronchiolitis, and (f) radiation recall pneumonitis. Published guidelines outline the treatment of ICI therapy-related pneumonitis based on the severity of symptoms. Treatment is often effective, although recurrence is possible. This article reviews the mechanism of ICIs and ICI therapy complications, with subsequent management techniques and illustrations of the various radiologic patterns of ICI-therapy related pneumonitis.©RSNA, 2019.

Association Between Maternal 2nd Trimester Plasma Folate Levels and Infant Bronchiolitis.

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (poverall = .112, pnonlinear effect = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Air pollution and acute respiratory infections among children 0-4 years of age: an 18-year time-series study.

Upper and lower respiratory infections are common in early childhood and may be exacerbated by air pollution. We investigated short-term changes in ambient air pollutant concentrations, including speciated particulate matter less than 2.5 µm in diameter (PM2.5), in relation to emergency department (ED) visits for respiratory infections in young children. Daily counts of ED visits for bronchitis and bronchiolitis (n = 80,399), pneumonia (n = 63,359), and upper respiratory infection (URI) (n = 359,246) among children 0-4 years of age were collected from hospitals in the Atlanta, Georgia, area for the period 1993-2010. Daily pollutant measurements were combined across monitoring stations using population weighting. In Poisson generalized linear models, 3-day moving average concentrations of ozone, nitrogen dioxide, and the organic carbon fraction of particulate matter less than 2.5 µm in diameter (PM2.5) were associated with ED visits for pneumonia and URI. Ozone associations were strongest and were observed at low (cold-season) concentrations; a 1-interquartile range increase predicted a 4% increase (95% confidence interval: 2%, 6%) in visits for URI and an 8% increase (95% confidence interval: 4%, 13%) in visits for pneumonia. Rate ratios tended to be higher in the 1- to 4-year age group compared with infants. Results suggest that primary traffic pollutants, ozone, and the organic carbon fraction of PM2.5 exacerbate upper and lower respiratory infections in early life, and that the carbon fraction of PM2.5 is a particularly harmful component of the ambient particulate matter mixture.

Bronchial and bronchiolar fibrosis in rats exposed to 2,3-pentanedione vapors: implications for bronchiolitis obliterans in humans.

2,3-Pentanedione (PD) is a component of artificial butter flavorings. The use of PD is increasing since diacetyl, a major butter flavorant, was associated with bronchiolitis obliterans (BO) in workers and has been removed from many products. Because the toxicity of inhaled PD is unknown, these studies were conducted to characterize the toxicity of inhaled PD across a range of concentrations in rodents. Male and female Wistar-Han rats and B6C3F1 mice were exposed to 0, 50, 100, or 200 ppm PD 6 h/d, 5 d/wk for up to 2 wk. Bronchoalveolar lavage fluid (BALF) was collected after 1, 3, 5, and 10 exposures, and histopathology was evaluated after 12 exposures. MCP-1, MCP-3, CRP, FGF-9, fibrinogen, and OSM were increased 2- to 9-fold in BALF of rats exposed for 5 and 10 days to 200 ppm. In mice, only fibrinogen was increased after 5 exposures to 200 ppm. The epithelium lining the respiratory tract was the site of toxicity in all mice and rats exposed to 200 ppm. Significantly, PD also caused both intraluminal and intramural fibrotic airway lesions in rats. The histopathological and biological changes observed in rats raise concerns that PD inhalation may cause BO in exposed humans.

Durvalumab-induced lesions of bronchiolitis and fully reversible bronchiectasis in a patient with non-small cell lung cancer: A case report.

Durvalumab is a humanized monoclonal antibody targeting programmed cell death ligand-1 (PD-L1), leading to an antitumor activity, used as consolidation therapy in patients with locally advanced unresectable non-small cell lung cancer (NSCLC). Several immune-related adverse events (irAEs) have previously been described in patients following treatment with immune checkpoint inhibitors (ICIs). To the best of our knowledge, we report the first case of immunotherapy-induced fully reversible bronchiolitis and bronchiectasis, despite the fact that its pathophysiological mechanism has been previously considered to be irreversible.

Influence of ambient air pollutant sources on clinical encounters for infant bronchiolitis.

RATIONALE: Data regarding the influence of ambient air pollution on infant bronchiolitis are few. OBJECTIVES: We evaluated the impact of several air pollutants and their sources on infant bronchiolitis. METHODS: Infants in the Georgia Air Basin of British Columbia with an inpatient or outpatient clinical encounter for bronchiolitis (n = 11,675) were matched on day of birth to as many as 10 control subjects. Exposure to particulate matter with a diameter of 2.5 mum or less (PM(2.5)), PM(10), NO(2)/NO, SO(2), CO, and O(3) were assessed on the basis of a regional monitoring network. Traffic exposure was assessed using regionally developed land use regression (LUR) models of NO(2), NO, PM(2.5), and black carbon as well as proximity to highways. Exposure to wood smoke and industrial emissions was also evaluated. Risk estimates were derived using conditional logistic regression and adjusted for infant sex and First Nations (Canadian government term for recognized aboriginal groups) status and for maternal education, age, income-level, parity, smoking during pregnancy, and initiation of breastfeeding. MEASUREMENTS AND MAIN RESULTS: An interquartile increase in lifetime exposure to NO(2), NO, SO(2), CO, wood-smoke exposure days, and point source emissions score was associated with increased risk of bronchiolitis (e.g., adjusted odds ratio [OR(adj)] NO(2), 95% confidence interval [CI], 1.12, 1.09-1.16; OR(adj) wood smoke, 95% CI, 1.08, 1.04-1.11). Infants who lived within 50 meters of a major highway had a 6% higher risk (1.06, 0.97-1.17). No adverse effect of increased exposure to PM(10), PM(2.5), or black carbon, was observed. Ozone exposure was negatively correlated with the other pollutants and negatively associated with the risk of bronchiolitis. CONCLUSIONS: Air pollutants from several sources may increase infant bronchiolitis requiring clinical care. Traffic, local point source emissions, and wood smoke may contribute to this disease.

[Two cases of lung injury due to inhalation of waterproofing spray--with special reference to pulmonary function disorder].

CASE 1: A 57-year-old man experienced severe dyspnea 24 hours after inhalation of waterproofing spray. Computed tomography (CT) revealed diffuse ground glass opacities in bilateral lungs. Pulmonary function tests showed mixed ventilatory disturbance with a low expiratory flow rate near the end of forced expiration and a normal diffusing capacity with normal functional residual capasity. The pulmonary function disorder was quickly improved by steroid therapy. CASE 2: A 59-year-old man smoked after inhaling waterproofing spray and soon developed dyspnea. The findings of CT were similar to those of case 1. His pulmonary function test revealed restrictive ventilatory disturbance and normal pulmonary diffusing capacity with low functional residual capacity. These findings improved without steroid treatment. However, it took more time for the pulmonary function to recover. There was probably specific inflammation around bronchioles, and the inflammation might have spread to the alveolar region in such cases with severe pulmonary function disorder. Steroid treatment seems to be useful to improve both the pulmonary function disorder and the clinical feature due to inhalation of waterproofing spray.

Chemical pneumonitis in a 9-year-old following chlorine gas exposure.

A previously fit and well 9-year-old boy developed shortness of breath and chest pain after playing with friends on a building site where bonfire materials were being collected. Firstline investigations failed to explain his symptoms, which worsened over the next 24 hours, necessitating endotracheal intubation and mechanical ventilation. When public health and the police retraced his steps, they found barrels of sodium hypochlorite and red diesel at the bonfire site, which when mixed had the potential to form chlorine gas leading to the diagnosis of a chemical pneumonitis secondary to chlorine gas inhalation. Supportive care was continued, and he was successfully extubated after 48 hours. At 6-week follow-up, he had no ongoing pulmonary symptoms.

[Effect of air pollution upon the hospitalization for acute lower respiratory tract infections among the Bucharest municipality's residents]. / Efectul poluarii aeriene asupra frecventei spitalizarii pentru infectii acute ale cailor respiratori inferioare în populatia municipiului Bucuresti.

OBJECTIVE: Assessment of the short-term association between exposure to outdoor air pollution and hospitalization for lower respiratory tract infections (LRTI) in the Bucharest municipality'spopulation. MATERIALS AND METHODS: Relation exposure--health effect has been explored through linear regression upon time series, where the independent variable was represented by daily levels of nitrogen dioxide (NO), carbon monoxide (CO), sulfur dioxide (SO2) and ozone (O3) from atmospheric air of Bucharest municipality whereas the dependent variable has been represented by daily frequency, by age groups, of Bucharest municipality residents, hospitalized during the year 2007for LRTI (ICD-10 codes: J12-J22). RESULTS: In the year 2007, through linear regression we found high correlations (p < 0.01) between the following variables: (a) daily atmospheric concentrations of NO2, CO and SO2, (b) daily frequencies of hospitalizations for LRTI by age group and (c) daily air levels of three of the above mentioned pollutants and the age-specific frequencies of patient hospitalization for LRTI. The O3 daily air levels have been correlated (p < 0.01) only with the daily air levels of SO2 and CO but wasn't correlated to NO2 air level or with the health effect studied CONCLUSIONS: in the Bucharest municipality, the study demonstrated robust associations between the atmospheric pollutants' levels and daily frequencies of hospital admissions for LRTI. Through inference the results suggests that the interventions for environment control which will result in decreasing of the pollution level with NO2, CO and SO2 might be associated with decreasing the frequency of hospitalization for LRTI and consequently with preserving the resources allocated for health.

Pregnancy Trimester-Specific Exposure to Ambient Air Pollution and Child Respiratory Health Outcomes in the First 2 Years of Life: Effect Modification by Maternal Pre-Pregnancy BMI.

Prenatal exposure to air pollution is associated with childhood respiratory health; however, no previous studies have examined maternal pre-pregnancy body mass index (BMI) as a potential effect modifier. We investigated whether maternal pre-pregnancy BMI modified the association of trimester-specific air pollution divided into quartiles of exposure (Q1⁻4) on respiratory health in the Growing Up in Singapore towards healthy Outcomes (GUSTO) study (n = 953) in 2-year-old children. For episodes of wheezing, children of overweight/obese mothers and who were exposed to particulate matter less than 2.5 µm (PM2.5) in the first trimester had an adjusted incidence rate ratio (IRR) (95% confidence interval (CI)) of 1.85 (1.23⁻2.78), 1.76 (1.08⁻2.85) and 1.90 (1.10⁻3.27) in quartile (Q) 2⁻4, with reference to Q1. This association is seen in the second trimester for bronchiolitis/bronchitis. The risk of ear infection in the first year of life was associated with exposure to PM2.5 in the first trimester with adjusted Odds Ratio (adjOR) (95% CI) = 7.64 (1.18⁻49.37), 11.37 (1.47⁻87.97) and 8.26 (1.13⁻60.29) for Q2⁻4, and similarly in the second year with adjOR (95% CI) = 3.28 (1.00⁻10.73) and 4.15 (1.05⁻16.36) for Q2⁻3. Prenatal exposure to air pollution has an enhanced impact on childhood respiratory health, and differs according to maternal pre-pregnancy BMI.

Exposure to acute air pollution and risk of bronchiolitis and otitis media for preterm and term infants.

Our aim is to estimate associations between acute increases in particulate matter with diameter of 2.5 µm or less (PM2.5) concentrations and risk of infant bronchiolitis and otitis media among Massachusetts births born 2001 through 2008.Our case-crossover study included 20,017 infant bronchiolitis and 42,336 otitis media clinical encounter visits. PM2.5 was modeled using satellite, remote sensing, meteorological and land use data. We applied conditional logistic regression to estimate odds ratios (ORs) and confidence intervals (CIs) per 10-µg/m3 increase in PM2.5. We assessed effect modification to determine the most susceptible subgroups. Infant bronchiolitis risk was elevated for PM2.5 exposure 1 day (OR = 1.07, 95% CI = 1.03-1.11) and 4 days (OR = 1.04, 95% CI = 0.99-1.08) prior to clinical encounter, but not 7 days. Non-significant associations with otitis media varied depending on lag. Preterm infants were at substantially increased risk of bronchiolitis 1 day prior to clinical encounter (OR = 1.17, 95% CI = 1.08-1.28) and otitis media 4 and 7 days prior to clinical encounter (OR = 1.09, 95% CI = 1.02-1.16 and OR = 1.08, 95% CI = 1.02-1.15, respectively). In conclusion, preterm infants are most susceptible to infant bronchiolitis and otitis media associated with acute PM2.5 exposures.

Progressive delayed respiratory complications of sulfur mustard poisoning in 43 Iranian veterans, three decades after exposure.

The most common delayed complication of sulfur mustard (SM) poisoning has been observed in the respiratory tracts. It was thus aimed to investigate the delayed respiratory complications in SM-exposed patients around 25 years before the study. Forty-three veterans with more than 25% disability of due to SM poisoning were investigated. Clinical examinations as well as pulmonary function test (PFT) were performed. High-resolution computed tomography (HRCT) of the lungs was done as clinically indicated. Triad of chronic cough, dyspnea, and expectoration were the most common symptoms that were recorded in 88.2%, 88.2%, and 64.7% of the patients, respectively. PFT abnormalities were detected in 44.18% of the patients. Restrictive pattern was the most common (41.86%), while pure obstructive pattern did not detect at all. Mixed pattern was significantly correlated with higher disability percentages among the veterans ( p < 0.001). Significant reverse correlation between the disability percentages and forced expiratory volume in 1 s/forced vital capacity ratio was obtained ( p = 0.010, r = -0.389). Air trapping was the most common abnormality in HRCTs (50%). Bronchiectasis (25%), pulmonary fibrosis (25%), and ground-glass attenuation (16.66%) were other common HRCT findings. Comparing with the previous studies on these patients, more restrictive and mixed pattern were observed. Moreover, bronchiolitis, bronchiectasis, and lung fibrosis were the main pathological findings in these patients.

Inhaled corticosteroids and long-acting beta 2-agonists in treatment of patients with chronic bronchiolitis following exposure to sulfur mustard.

We examined the role of two regimens of combination inhaler therapy on amount of reversibility of chronic lung complications in mustard gas exposed patients. In a phase III, prospective, randomized clinical trial, 105 participants received either combination form of fluticasone propionate and salmetrol, 500/100 microg daily (group 1; n = 52) or beclomethasone, 1000 microg daily, and salbutamol inhaler, 800 microg daily (group 2; n = 53) for 12 wk. Pulmonary function test (PFT) indices and respiratory symptoms (including dyspnea, night awakening due to dyspnea and cough) were assessed at baseline and in each visit. Thirty-six patients in group 1 and 30 patients in group 2 completed study course. Both medication regimes increased pretreatment forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC%, and peak expiratory force (PEF) by the end of 12 wk. It seems that these improvements are more constant in group 1 than in group 2. Reversibility, that is, 10% increase of FEV1 in the second month was seen for 27% of patients in the group 1 and for 7% in the group 2. VAS scores have decreased in two groups during treatment period (p = .003) and after follow-up period it remained sustained in group 1 alone. Inhaled corticosteroids and long-acting beta 2-agonists are effective in treatment of patients with chronic bronchiolitis following exposure to sulfur mustard. However, a medium dose of fluticasone/salmeterol has the same effect on the airways reversibility, rather than a very high dose of beclomethasone with only the short-acting beta-agonist.

Long term consequences from exposure to sulfur mustard: a review.

Mustard gas (HD) was a widely used chemical warfare agent during World War I and more recently in the Iraq-Iran war (1980-1988). To date, dramatically, 45,000 Iranians are suffering from late respiratory complications due to MG exposure. This review covers two decades of researches on latent pulmonary effects of MG. Findings from clinical manifestations, pathologic examinations, laboratory data, lung function tests, and radiological evaluations are reviewed. From this review we are able to provide a suitable practical plan for workup and management of patients in this setting.

Apoptosis and necrosis are involved in the toxicity of Sauropus androgynus in an in vitro study.

BACKGROUND/PURPOSE: The raw juice of the young sticks and leaves of Sauropus androgynus (SA) has been widely used as a natural food for body weight reduction and vision protection in Taiwan and Southeast Asia. But as has been reported, SA-associated obliterative bronchiolitis can develop after taking SA for more than 3 months. Lung transplantation was carried out in severe cases. METHODS: To study the toxic effect, we separated the SA extract into three parts, namely CHCl3, EtOAc and n-BuOH fractions, using polarity dissection. NIH3T3 fibroblasts were treated with the SA fractions 300 microg/mL and subjected to a series of cytotoxic assays. RESULTS: The EtOAc fraction exhibited the strongest effect of cell growth inhibition, followed by the CHCl3 and n-BuOH fractions. Features of condensed chromatin and apoptosis were observed in cells exposed to n-BuOH and EtOAc fractions using fluorescence microscopy. Formation of DNA ladders was also observed in the above cells. Instead, the CHCl3 fraction induced DNA smearing. In bivariate dot plots of annexin V and propidium iodide double staining, necrosis and apoptosis appeared in cells treated with CHCl3 and n-BuOH fractions, respectively, and a mixed type of necrosis and apoptosis appeared in EtOAc fraction-treated cells. CONCLUSION: Our results indicate that necrosis and apoptosis are involved in the toxic effect of SA in NIH3T3 fibroblasts. More evidence is needed to clarify if necrosis and apoptosis are also related to the pathogenesis of SA-associated obliterative bronchiolitis.