Immunotherapy-Induced Airway Disease: A New Pattern of Lung Toxicity of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been shown to improve overall and progression-free survival in various cancers but have been associated with various immune-related adverse events (IRAEs), including interstitial lung disease, especially organizing pneumonia. We report 2 cases of isolated severe airway disease attributable to ICIs, a rarely reported pattern of lung toxicity. The first patient received nivolumab with or without ipilimumab in a randomized double-blind trial for locoregional metastatic melanoma. The second patient was treated with nivolumab for lung adenocarcinoma. An IRAE was suspected in both cases due to a temporal relationship between ICI initiation and symptom onset. ICIs were stopped, and high-dose prednisone, inhaled corticosteroids, and bronchodilators were administered, allowing a rapid clinical and functional improvement in Patient 1. In Patient 2, despite prolonged high-dose prednisone, only a stabilization of forced expiratory volume in 1 s could be achieved, and the disease course was complicated by respiratory infections resulting in further loss of lung function. The patient died 1 year later due to progression of metastatic disease. These 2 cases suggest that pulmonary IRAEs secondary to ICIs may present as isolated bronchitis or bronchiolitis, with variable outcomes following ICI withdrawal and systemic corticosteroids.

Case report of severe bronchial web-like stenoses after 'surviving the unsurvivable'.

BACKGROUND: There are few cases of multiple bronchial stenoses reported in the literature and none of the severity described here. The case is relevant due to its rareness, the pathophysiological insights derived, the successful interventional pulmonology strategies demonstrated, and as an example of a rare indication for high-risk lung transplantation. CASE PRESENTATION: A 47-year-old man developed multiple recurrent bronchial web-like stenoses five weeks after an episode of severe tracheo-bronchitis presumed secondary to a chemical inhalation injury which initially caused complete bilateral lung collapse necessitating veno-venous extracorporeal membrane oxygenation. The stenoses completely effaced bronchi in many locations causing severe type II respiratory failure requiring mechanical ventilation and bronchoscopic puncture / dilatation then ultimately bilateral lung transplantation. CONCLUSION: This very rare case highlights the morbid sequelae that can arise after catastrophic tracheobronchitis which now, in the era of extracorporeal membrane oxygenation, may be survivable in the short-term.

Anaphylactoid-like Reaction to Midazolam During Oral and Maxillofacial Surgery.

We experienced a case of life-threatening hypotension and bronchoconstriction associated with edema in a patient undergoing resection of a tumor of the right mandible following intravenous midazolam for induction of general anesthesia. We decided to postpone surgery for further examination of a possible drug-induced allergic reaction, and we rescheduled surgery for 1 week later. After administering H1 and H2 histamine antagonists, we administered a slow induction with sevoflurane in nitrous oxide and oxygen plus intravenous atropine sulfate after performing a test dose injection. We safely induced and maintained anesthesia with nitrous oxide, oxygen, and sevoflurane.

Tracheobronchial calcifications in children.

BACKGROUND: Tracheobronchial calcifications are considered a rare radiologic finding in children. Our clinical experience indicates that this finding is not infrequently seen among children with prosthetic heart valves who have been treated with warfarin sodium. OBJECTIVE: We hypothesized that calcifications of the tracheobronchial tree are more common than previously reported in this patient population. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of children who underwent cardiac valve replacement at our institution to estimate the prevalence. RESULTS: Tracheobronchial calcifications were identified on chest radiographs in 6 out of 17 children (35%), indicating that this imaging finding might be frequently overlooked. CONCLUSION: All children positive for tracheobronchial calcifications had been anticoagulated with warfarin sodium between the time of surgery and development of positive imaging findings. Our findings suggest that tracheobronchial calcifications are not uncommon in children treated with warfarin. Further investigation is necessary to determine wether there is a cause-effect relationship in these children.

[Peculiarities of bronchopulmonary pathology in copper industry workers in the Kola High North].

A survey of 1097 workers of metallurgical enterprises showed that a chronic bronchitis is the most common bronchopulmonary disease (8,8-13,3%) in copper production workers There are much less detected chronic obstructive pulmonary disease (0.8-1.7%), asthma (0.3-0.4%), and only in copper-smelting plant workers - a toxic chemical pneumosclerosis (0.6%). Working conditions determine a higher prevalence of respiratory diseases and their development in less industrial work record in the manufacturing workers employed in electrolytic processing of copper and auxiliary shops. The conclusion about the need to improve working conditions and the use of more effective personal respiratory protection devices for copper production workers has been made.

Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia.

Epidemiological studies have established a positive correlation between human mortality and increased concentration of airborne particulate matters (PM). However, the mechanisms underlying PM related human diseases, as well as the molecules and pathways mediating the cellular response to PM, are not fully understood. This study aims to investigate the global gene expression changes in human cells exposed to PM(10) and to identify genes and pathways that may contribute to PM related adverse health effects. Human bronchial epithelial cells were exposed to PM(10) collected from Saudi Arabia for 1 or 4 days, and whole transcript expression was profiled using the GeneChip human gene 1.0 ST array. A total of 140 and 230 genes were identified that significantly changed more than 1.5 fold after PM(10) exposure for 1 or 4 days, respectively. Ingenuity Pathway Analysis revealed that different exposure durations triggered distinct pathways. Genes involved in NRF2-mediated response to oxidative stress were up-regulated after 1 day exposure. In contrast, cells exposed for 4 days exhibited significant changes in genes related to cholesterol and lipid synthesis pathways. These observed changes in cellular oxidative stress and lipid synthesis might contribute to PM related respiratory and cardiovascular disease.

Chlorine-induced extensive tracheobronchial necrosis concomitantly benzene-induced pancytopenia presented with severe pneumonia.

We report a case of 25-year-old woman with severe tracheobronchial necrosis caused by chlorine released from a mixture household cleaning agents. She subsequently exposed benzene while she was fixing the seats with benzene containing gum. The case was found interesting with its history, delayed diagnosis, bronchoscopic features, and fatal outcome. We presented its bronchoscopic and pathological images which has not been shown in the literature up to date.

An observational study of the role of indoor air pollution in pets with naturally acquired bronchial/lung disease.

BACKGROUND: Indoor air pollution (IAP) is an emerging issue for both human and veterinary patients under the concept of 'One Health'. The association between IAP and respiratory disease in companion animals has been reported. OBJECTIVES: The present study investigated the relationship between quantifiable indoor air quality and clinical characteristics of naturally acquired bronchial/lung disease in pet dogs and cats. METHODS: A total of 36 clinical cases (20 dogs and 16 cats) with naturally acquired bronchial/lung disease were prospectively recruited. Lower airway samples were collected and analysed, and clinical signs and the information from pulmonary function testing were examined. Indoor air quality was estimated by the average concentration of particles measuring ≤2.5 µm (PM2.5, µg/m3 ) and volatile organic compounds (VOC, ppm) in the animals' domestic microenvironments. RESULTS: Exposure to IAP was not found to be correlated with the severity of clinical signs, pulmonary function changes or bronchoalveolar lavage fluid cytology in cats with bronchial/lung disease. However, a hypercellular response in canine lower airways was found to be associated with poor indoor air quality, including unacceptable indoor PM2.5 levels (>35 µg/m3 ) or increases in VOC concentration (>1 ppm) in places most commonly frequented by the dogs in the home. CONCLUSIONS: Poor indoor air quality may exacerbate airway disease in pets and should not be ignored in modern society.

[Bronchopulmonary diseases features in miners of Kolsky Transpolar area].

Miners engaged into open-cast and underground extraction of copper-nickel ores in Kolsky Transpolar area have chronic bronchitis as a main nosologic entity among chronic bronchopulmonary diseases (19.1% of the workers). Considerably lower (4.0% of the workers) occurrence concerns chronic obstructive lung disease and bronchial asthma, both developed before the occupational involvement (1.3% of the workers). Complex of occupational and nonoccupational risk factors is connected mostly with smoking that increases COLD/CB risk 10.7-15.8-fold.

Endobronchial Manifestation of Methotrexate-induced Lymphoproliferative Disorder.

Lymphoproliferative disorders can occur in patients with autoimmune disorders who undergo long-term methotrexate therapy (MTX-LPD). Although the manifestations of MTX-LPD are diverse, little attention is paid to endobronchial involvement. We herein describe two patients with MTX-LPD who presented with parenchymal pulmonary tumors and endobronchial involvement of LPD; one had lymphomatoid gramulomatosis and the other LPD. The patients had no tumors adjacent to the endobronchial lesions. The endobronchial findings included multiple protruded mucosal lesions covered with white material, which was pathologically consistent with LPD. Recognition of the findings may help in making an earlier diagnosis of MTX-LPD in appropriate settings.

Afghanistan Particulate Matter Enhances Pro-Inflammatory Responses in IL-13-Exposed Human Airway Epithelium via TLR2 Signaling.

Since the start of Afghanistan combat operations in 2001, there has been an increase in complaints of respiratory illnesses in deployed soldiers with no previous history of lung disorders. It is postulated that deployment-related respiratory illnesses are the result of inhalation of desert particulate matter (PM) potentially acting in combination with exposure to other pro-inflammatory compounds. Why some, but not all, soldiers develop respiratory diseases remains unclear. Our goal was to investigate if human airway epithelial cells primed with IL-13, a type 2 inflammatory cytokine, demonstrate stronger pro-inflammatory responses to Afghanistan desert PM (APM). Primary human brushed bronchial epithelial cells from non-deployed, healthy subjects were exposed to APM, both with and without IL-13 pretreatment. APM exposure in conjunction with IL-13 resulted in significantly increased expression of IL-8, a pro-inflammatory cytokine involved in neutrophil recruitment and activation. Furthermore, expression of TLR2 mRNA was increased after combined IL-13 and APM exposure. siRNA-mediated TLR2 knockdown dampened IL-8 production after exposure to APM with IL-13. APM with IL-13 treatment increased IRAK-1 (a downstream signaling molecule of TLR2 signaling) activation, while IRAK-1 knockdown effectively eliminated the IL-8 response to APM and IL-13. Our data suggest that APM exposure may promote neutrophilic inflammation in airways with a type 2 cytokine milieu.

Side effect profile and tolerability of adenosine myocardial perfusion scintigraphy in patients with mild asthma or chronic obstructive pulmonary disease.

BACKGROUND: Adenosine may cause bronchoconstriction in subjects with asthma or chronic obstructive pulmonary disease (COPD). Recent evidence suggests that this effect may be dependent on the severity of disease. This study investigates the tolerability of adenosine stress in patients with mild asthma or COPD undergoing myocardial perfusion scintigraphy. METHODS AND RESULTS: In this case-control study patients with known or suspected mild asthma or COPD were pretreated with an inhaled beta(2)-adrenergic agonist and adenosine titrated up to the maximal dose of 140 microg x kg(-1) x min(-1) over a period of 6 minutes. The occurrence of side effects and test tolerability were compared between the airway disease group and 72 control subjects. Of 1261 patients, 124 had known or suspected airway disease; of these, 72 (58%) were suitable for adenosine stress. The proportion of tests completed as per protocol in the asthma/COPD group was similar to that of control subjects (93% vs 100%, P = .06). Dyspnea (n = 38 [53%] in asthma/COPD group vs n = 25 [35%] in control group, P = .03) and chest pain (n = 14 [19%] in asthma/COPD group vs n = 16 [22%] in control group, P = .7) were the most common side effects, and these were mostly mild and well tolerated. Bronchospasm occurred in 5 patients with asthma/COPD but reverted shortly after discontinuation of the adenosine infusion. Aminophylline was not required in any case. CONCLUSIONS: A stepwise 6-minute adenosine infusion with prophylactic beta(2)-adrenergic agonist is safe and well tolerated in patients with mild asthma or COPD.

Fatal mephenesin intoxication.

This report describes a death related to the abuse of and intoxication by mephenesin. To the best of our knowledge, this is the first report case of lethal intoxication involving solely mephenesin and reporting mephenesin blood concentrations. The victim was a 48-year-old woman found unconscious at home. Resuscitation was unsuccessful. Toxicological analysis was performed on a blood sample collected during resuscitation. The results being negative, the body was exhumed for an autopsy, which revealed bronchial inhalation syndrome. Analysis in a second laboratory has revealed the presence of mephenesin in samples collected during autopsy. No other drug/toxin was found, and alcohol was negative. Reanalysis of the peripheral blood collected during resuscitation found a mephenesin concentration of 15.81 microg/mL (15-fold greater that the maximum concentration that would result from a single intake of a 500 mg formulation). The pathologist has concluded on a bronchial inhalation syndrome consecutive to a mephenesin overdose as the cause of death. The manner of this death is discussed in the light of the toxicological hair analysis and the medical past of the victim.

Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian "mustard lung" patients.

A unique chronic obstructive pulmonary disease (COPD), provisionally called "mustard lung", which occurs as a late complication of sulfur mustard (SM) exposure among SM-exposed Iranians, is presently poorly characterized. This investigation evaluates p53 immunoreactivity in bronchial epithelium of individuals with histories of tobacco use and/or SM exposure, as a tool to help define mustard lung. In this study, 68 COPD patients were segregated into two groups, 35 mustard-exposed patients (including 8 smokers) and 33 unexposed patients (including 16 smokers). Disease severity was assessed with pulmonary function tests. p53 protein in bronchial tissue obtained as biopsies was quantitated by immunostaining. Among nonsmokers, 41.2% of unexposed subjects and 14.8% of exposed subjects expressed p53. Among smokers, 25% of the unexposed group and 50% of the exposed group expressed the protein. Initial data trends suggest an additive contribution of SM exposure and smoking to p53 immunoreactivity. These results illustrate the use of p53 immunoreactivity in the characterization of COPD, including mustard lung.

Tracheobronchopathy From Inhaled Corticosteroids.

Inhaled corticosteroids (ICSs) have become the mainstay of asthma control. They are also recommended as an add-on therapy to long-acting beta agonists and anticholinergics in moderate to severe COPD with recurrent exacerbations. Ultimately this clinical practice has led to the widespread use of ICSs, which are supported by a more favorable side effect profile than that of systemic steroids.