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.

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.

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.

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.

Noninfectious Generalized Bronchiolitis in the Setting of Allogeneic Stem Cell Transplantation: A Potential Mimic of Lower Respiratory Tract Infection.

RATIONALE AND OBJECTIVES: To describe a little-known therapy-related small-airway phenomenon presumably caused by mucosal irritation in patients undergoing allogeneic stem cell transplantation (allo-SCT). MATERIALS AND METHODS: Retrospective database search at our institution identified 739 hematologic patients who underwent chemotherapy + allo-SCT between September 2004 and March 2014. After infectious pulmonary complications were excluded, 75 patients (female = 24; male = 51; median age = 47 years) with signs of generalized bronchiolitis (GB) on chest high-resolution computed tomography were identified. Computed tomography (CT) was performed proximate to chemotherapy onset; 92% had follow-up CT (mean, 1.9 weeks). The presence of centrilobular nodules, bronchial wall thickening (BWT), tree-in-bud (distributed diffuse vs. focal), ground-glass opacity, airspace opacification, luminal impactions, and air trapping was correlated with occurrence and duration of oral mucositis and therapy characteristics. Intensity of tree-in-bud and centrilobular nodules was graded absent (grade = 0), moderate (grade = 1), or marked (grade = 2). RESULTS: Overall incidence of GB among allo-SCT patients was 10.14%. GB was diagnosed at the time point of transplantation with a mean duration of CT findings of 4 weeks (±2.7). Tree-in-bud (17% [grade 2] and 83% [grade 1]) and BWT were present in 100% of the patients. Centrilobular nodules diffusely distributed were found in 45.5% of patients (20% [grade 2], 24% [grade 1], and 56% [none]). Air trapping and mosaic pattern were found in 13% and 16% of the patients, respectively. Resolution of GB was spontaneous. GB and its severity correlated with the temporal course and grade of oral mucositis; frequency and degree were not significantly influenced by the chemotherapy regimen. The incidence of GB in high-resolution computed tomography was statistically and significantly higher in patients with oral mucositis (P < 0.035). CONCLUSIONS: GB is frequent during chemotherapy for allo-SCT and is characterized by an even distribution of tree-in-bud, BWT, centrilobular nodules, mild clinical symptoms, and spontaneous resolution.

Inhalación masiva de amoniaco: reporte de dos casos / Massive ammonia inhalation: report of two cases

Ammonia (NH3) is an irritant and corrosive gas whose inhalation at high concentrations mainly occurs during agricultural and industrial activities, as occupational accidents. The extent and severity of the damage depends on the concentration and time of exposure to the toxic, which can cause skin, eye, respiratory and life-threatening injuries. We present two cases of patients acutely exposed to high concentrations of NH3. Both patients survived to the acute phase of the respiratory injury, but developed chronic lung derangements.

El amoniaco (NH3) es un gas irritante y corrosivo cuya inhalación aguda en altas concentraciones se produce principalmente durante accidentes laborales en el sector agrícola e industrial. La extensión y severidad del daño depende de la concentración y tiempo de exposición al tóxico, el cual puede causar lesiones a nivel cutáneo, ocular, respiratorio y riesgo vital. Presentamos dos casos de pacientes expuestos en forma aguda a NH3 en altas concentraciones. Ambos pacientes sobrevivieron a la fase aguda y evolucionaron con lesiones respiratorias crónicas.

Short-term risk of hospitalization for asthma or bronchiolitis in children living near an aluminum smelter.

Few studies have measured the effect of short-term exposure to industrial emissions on the respiratory health of children. Here we estimate the risk of hospitalization for asthma and bronchiolitis in young children associated with their recent exposure to emissions from an aluminum smelter. We used a case-crossover design to assess the risk of hospitalization, February 1999-December 2008, in relation to short-term variation in levels of exposure among children 0-4 years old living less than 7.5 km from the smelter. The percentage of hours per day that the residence of a hospitalized child was in the shadow of winds crossing the smelter was used to estimate the effect of wind-borne emissions on case and crossover days. Community-wide pollutant exposure was estimated through daily mean and daily maximum SO2 and PM2.5 concentrations measured at a fixed monitoring site near the smelter. Odds ratios (OR) were estimated using conditional logistic regressions. The risk of same-day hospitalization for asthma or bronchiolitis increased with the percentage of hours in a day that a child's residence was downwind of the smelter. For children aged 2-4 years, the OR was 1.27 (95% CI=1.03-1.56; n=103 hospitalizations), for an interquartile range (IQR) of 21% of hours being downwind. In this age group, the OR with PM2.5 daily mean levels was slightly smaller than with the hours downwind (OR: 1.22 for an IQR of 15.7 µg/m(3), 95% CI=1.03-1.44; n=94 hospitalizations). Trends were observed between hospitalizations and levels of SO2 for children 2-4 years old. Increasing short-term exposure to emissions from a Quebec aluminum smelter was associated with an increased risk of hospitalization for asthma and bronchiolitis in young children who live nearby. Estimating exposure through records of wind direction allows for the integration of exposure to all pollutants carried from the smelter stack.

Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma.

We present the case of a 62-year-old Japanese woman with relapsed adult T-cell leukemia/lymphoma (ATLL) who was treated with humanized anti-CCR4 monoclonal antibody (KW-0761). Although this antibody was highly effective against refractory ATLL, 6 months after the final KW-0761 infusion, the patient complained of hypoxia due to diffuse panbronchiolitis. Physicians should remain vigilant to the possibility of such previously unreported late-onset adverse effects associated with KW-0761 therapy.

Lung morphology and growth of rats exposed to tobacco smoke and alcohol.

PURPOSE: Investigate the morphological effects of chronic exposure to tobacco smoke inhalation and alcohol consumption on the lungs and on the growth of rats. METHODS: Sixty male Wistar rats were divided into four groups: control, tobacco, alcohol, tobacco + alcohol, for a period of study 260 days. Morphological analysis was conducted by optical and electron microscopy. Rat growth was investigated by measuring the snout-anus length, body mass index and body weight. RESULTS: The three groups exposed to the drugs presented lower growth and lower weight than the control group. The percentages of alveolitis, bronchiolitis and the mean alveolar diameter were greater, particularly in the groups exposed to tobacco smoke, but were not significantly different from the control group. Electron microscopy revealed more intense apoptotic and degenerative lesions in the smoking group, while degenerative lesions in the lamellar bodies were more intense with the association of both drugs. CONCLUSIONS: This experimental model showed morphological alterations observed by electron microscopy, principally due to tobacco smoke exposure. Alcohol and tobacco hindered the growth of rats, such that tobacco showed a greater effect on body length and alcohol on body weight.

Lung morphology and growth of rats exposed to tobacco smoke and alcohol / Estudo morfológico dos pulmões e crescimento de ratos expostos à fumaça do cigarro e ao álcool

PURPOSE: Investigate the morphological effects of chronic exposure to tobacco smoke inhalation and alcohol consumption on the lungs and on the growth of rats. METHODS: Sixty male Wistar rats were divided into four groups: control, tobacco, alcohol, tobacco + alcohol, for a period of study 260 days. Morphological analysis was conducted by optical and electron microscopy. Rat growth was investigated by measuring the snout-anus length, body mass index and body weight. RESULTS: The three groups exposed to the drugs presented lower growth and lower weight than the control group. The percentages of alveolitis, bronchiolitis and the mean alveolar diameter were greater, particularly in the groups exposed to tobacco smoke, but were not significantly different from the control group. Electron microscopy revealed more intense apoptotic and degenerative lesions in the smoking group, while degenerative lesions in the lamellar bodies were more intense with the association of both drugs. CONCLUSIONS: This experimental model showed morphological alterations observed by electron microscopy, principally due to tobacco smoke exposure. Alcohol and tobacco hindered the growth of rats, such that tobacco showed a greater effect on body length and alcohol on body weight.

OBJETIVO: Investigar os efeitos morfológicos da exposição crônica à inalação de fumaça do tabaco e o do consumo de álcool nos pulmões e no crescimento de ratos. MÉTODOS: Sessenta ratos Wistar machos foram distribuídos em quatro grupos: controle, tabaco, álcool e tabaco + álcool, e acompanhados por um período de 260 dias. No final do periodo foi realizada análise morfológica dos pulmões por microscopia óptica e eletrônica. O crescimento dos ratos foi investigado através da medição do comprimento focinho-ânus, peso corporal e índice de massa corporal. RESULTADOS: Os três grupos expostos às drogas apresentaram peso e comprimento significativamente menores que os do grupo controle. As percentagens de bronquiolite e alveolite, e o diâmetro alveolar médio foram maiores nos grupos expostos à fumaça do tabaco, mas sem significancia estatística quando comparadas ao grupo controle. A microscopia eletrônica revelou apoptose mais intensa e lesões degenerativas no grupo de fumantes, enquanto lesões degenerativas nos corpos lamelares foram mais intensas com a associação de ambas as drogas. CONCLUSÕES: Este modelo experimental mostrou alterações morfológicas observadas por microscopia eletrônica, principalmente devido à exposição ao tabaco. Tanto o alcool como o tabaco prejudicaram o crescimento dos animais, o tabaco mostrando um efeito maior sobre o comprimento e o álcool sobre o peso corporal.

A randomized controlled trial of propranolol for infantile hemangiomas.

OBJECTIVE: Propranolol hydrochloride is a safe and effective medication for treating infantile hemangiomas (IHs), with decreases in IH volume, color, and elevation. METHODS: Forty children between the ages of 9 weeks and 5 years with facial IHs or IHs in sites with the potential for disfigurement were randomly assigned to receive propranolol or placebo oral solution 2 mg/kg per day divided 3 times daily for 6 months. Baseline electrocardiogram, echocardiogram, and laboratory evaluations were performed. Monitoring of heart rate, blood pressure, and blood glucose was performed at each visit. Children younger than 6 months were admitted to the hospital for monitoring after their first dose at weeks 1 and 2. Efficacy was assessed by performing blinded volume measurements at weeks 0, 4, 8, 12, 16, 20, and 24 and blinded investigator scoring of photographs at weeks 0, 12, and 24. RESULTS: IH growth stopped by week 4 in the propranolol group. Significant differences in the percent change in volume were seen between groups, with the largest difference at week 12. Significant decrease in IH redness and elevation occurred in the propranolol group at weeks 12 and 24 (P = .01 and .001, respectively). No significant hypoglycemia, hypotension, or bradycardia occurred. One child discontinued the study because of an upper respiratory tract infection. Other adverse events included bronchiolitis, gastroenteritis, streptococcal infection, cool extremities, dental caries, and sleep disturbance. CONCLUSION: Propranolol hydrochloride administered orally at 2 mg/kg per day reduced the volume, color, and elevation of focal and segmental IH in infants younger than 6 months and children up to 5 years of age.

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.

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.

[A case of bronchiolitis possibly associated with inhalation of hard metal].

A 36-year-old man, a worker exposed to tungsten and cobalt compounds, was admitted because of chest bilateral micronodular shadow with chronic cough and sputum. Chronic sinusitis, mild hypoxemia, obstructive respiratory impairment and chest radiological findings fulfilled the Japanese diagnostic criteria for diffuse panbronchiolitis, while atypical bronchoalveolar lavage fluid and pathological findings were seen. The surgical lung biopsy specimens showed patchy centrilobular inflammatory change with monocytic infiltrations and particulate deposition inside the area of bronchiolitis, but neither tungsten nor cobalt was found. Treatment with a macrolide antibiotic had no effect on the patient's symptoms, hypoxemia and lung function, suggesting bronchiolitis associated with inhalation of hard metal.

Fire-eater's pneumonitis.

The authors report a case of acute respiratory failure that fulfils the diagnostic criteria for fire-eater's pneumonitis; pathological features, usually described only in experimental works on animals, are also discussed.

[Octafluoropropane inhalation toxicity].

Wistar rats were used to study inhalation toxicity of octafluoropropane (OFP, freon-218) at the following concentration: 300 g/m3 (4-hrs), 30 g/m3 (0.5 to 4 hrs), 3 g/m3 (8 hrs), and 0.3 g/m3 (16 hrs). According to the histological analysis, OFP at the concentrations of 300 and 30 g/m3 had a politrophic toxic effect. Target organs were the lung, trachea, bronchus, heart, kidney, and the adrenaL There were dystrophic and necrobiotic lesions in the upper airways epithelium. Subacute and chronic vesicular bronchiolitis developed on days 7 and 14, respectively. Visceral organs and brain were found plethoric and the lung was found hemorrhagic. Similar lesions were seen in the trachea, bronchus, lung, liver, spleen, kidney, adrenal, heart, and the brain. Lipid redistribution was observed in the adrenal cortex and vascular reactions of renal tissue with juxtamedullar blood shunting. Toxicity of small OFP concentrations (3 and 0.3 g/m3) was distinguished by an extended aftereffect, these concentrations did not cause visible pathomorphologic changes but gave rise to an extended pathologic process detectable by biochemistry. In all concentrations, OFP impacted erythrocyte metabolism changing the lipid composition of cell membrane and activating membrane-bound adenosinetriphos-phatases. The activities of hepatocyte and myocardiac cytoplasmatic enzymes were altered in blood plasma. Increased malonic dialdehyde in blood plasma and decreased cell antioxidant GSH in erythrocytes suggested exaggerated lipid peroxidation. These data point to the necessity of revising the existing limits for OFP concentrations in air of populated areas, working areas, and closed human environments.

Pulmonary involvement in systemic sclerosis due to therapy and as a complication.

Lung involvement frequently occurs in systemic sclerosis (SS), similar to other connective tissue diseases. Sometimes lung disease may be a side effect of antirheumathic drugs. We report a case of a patient affected by SS, with isolated pulmonary hypertension, who developed bronchiolitis secondary to penicillamine. The latter was treated by withdraw of the drug without increasing the steroids. After one month, the patient's clinical conditions appeared improved.