Chemical Pneumonitis Research Articles

Radiation pneumonitis and early circulatory cytokine markers

Radiation pneumonitis is a distinct clinical entity that differs from other pulmonary symptoms such as allergic pneumonitis, chemical pneumonitis, or pneumonia by various infectious agents. Recent research has supported the mechanism of cellular interaction between lung parenchymal cells and circulating immune cells mediated through a variety of cytokines including proinflammatory cytokines, chemokines, adhesion molecules, and profibrotic cytokines. Identifying reliable biomarkers for radiation pneumonitis will allow us to identify individuals at risk for pneumonitis before or during the early stage of therapy. Prospective blood sampling, scoring of respiratory symptoms, and chest imaging were conducted for patients receiving thoracic radiotherapy for malignancy. Serial plasma specimens were analyzed for circulating cytokine changes before, during, and up to 12 weeks after radiation. Radiation pneumonitis was diagnosed using National Cancer Institute (NCI) common toxicity criteria. Cytokine analysis was assayed for interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), E-selectin, L-selectin, transforming growth factor beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) using enzyme linked immmunosorbant assay (ELISA). Twenty-four patients had clinical follow-up longer than 12 months after radiotherapy. Thirteen had symptomatic pneumonitis (NCI grade 2). The peak incidence of symptoms was between 6 and 13 weeks after radiotherapy. Six patients had only radiographic infiltrates (NCI grade 1). Five patients did not have clinical or radiographic pneumonitis. Both IL-1alpha and IL-6 levels were significantly higher before, during, and after radiotherapy for those who had pneumonitis. The pattern of changes of MCP-1, E-selectin, L-selectin, TGF-beta1, and bFGF varied, but none of these cytokines correlated with radiation pneumonitis. Analysis of a panel of circulating cytokines with different putative functions in radiation pulmonary injury identified IL-1alpha and IL-6 as early circulating cytokine markers for radiation pneumonitis.

ELECTROPHYSIOLOGICAL AND HISTOPATHOLOGICAL EVALUATION OF RESPIRATORY TRACT, DIAPHRAGM, AND PHRENIC NERVE AFTER DICHLORVOS INHALATION IN RATS

The aim of this study was to investigate the dose-related effects of dichlorvos inhalation on electrophysiological alterations of diaphragm and phrenic nerve and the changes in the histologic structure of respiratory system. This study was performed on 33 rats divided into 5 groups, inhaling 1, 2, 5, 10, and 15 µg/L of dichlorvos, respectively. Electrodiagnostic investigations of diaphragm and phrenic nerve were made before and after inhalations. Aspiration samples were taken from lungs to evaluate the presence of infection agents. The airways, lungs, and diaphragms were dissected out for histologic investigation. Rats exposed to a low concentration of dichlorvos (1-5 µg/L) showed no symptoms of intoxication, but exposure to higher doses (10-15 µg/L) induced dyspnea in several animals. Lower doses of dichlorvos revealed no electromyographic changes on diaphragm, whereas higher doses revealed a clear neuropathic involvement. Delayed phrenic nerve motor conduction velocity was noted for each group (p < .05). Morphologic changes on the tracheal epithelium, hyperplasia, thickening of the blood-air barrier, degeneration in alveoli, and ductus alveolaris were seen in histopathologic investigation. In conclusion, the acute inhalation of dichlorvos caused clear evidence of neuropathic involvement of the diaphragm and the phrenic nerve. Also, toxic pneumonitis and injury to the tracheal epithelial were noticed.

Protection of the lungs from acid during aspiration

Unlike the thick mucosa that normally covers the upper gastrointestinal tract, the membranes that cover the distal surfaces of the lungs are remarkably attenuated. This permits rapid exchange of gases between the airspaces and pulmonary vasculature, and may make the lungs more susceptible to acid challenges associated with acid reflux and aspiration. Any injury to the alveolar epithelium could result in the movement of solute and water into the airspaces (chemical pneumonia) and impair gas exchange. In this study, we used a fluorescent approach to compare the relative permeability of the apical basolateral surfaces of the lungs to the exchange of the ionic forms of acids and bases. The apical membranes proved to be much less permeable to NH 4 + and HCO 3 + than the basolateral membranes. This asymmetry in permeability should enhance resistance of the epithelium to inspired acidic challenges by slowing entry of acid into the cells and by linking the intracellular pH of the alveolar cells to that of the plasma, which is a relatively large, well-buffered compartment. Evidence also was obtained that the acid is secreted by the membranes covering the lungs.

Imaging of occupational lung disease.

Occupational lung disease comprises a wide variety of disorders caused by the inhalation or ingestion of dust particles or noxious chemicals. These disorders include pneumoconiosis, asbestos-related pleural and parenchymal disease, chemical pneumonitis, occupational infection, hypersensitivity pneumonitis, and organic dust toxic syndrome. Most of these disorders produce diffuse lung disease. Although many of the disorders can be detected at chest radiography, high-resolution computed tomography (CT) has been shown to be superior to chest radiography in depicting parenchymal, airway, and pleural abnormalities. Some occupational lung diseases have characteristic radiologic features suggesting the correct diagnosis, whereas in others, a combination of clinical features, related occupational history, radiologic findings, and literature supporting an association between the exposure and the disease process is required for diagnosis. With advances in chest radiology, including high-resolution CT, radiologists play a key role in the clinical evaluation of occupational lung diseases and should continue their involvement in the diagnosis and treatment of these diseases.

Surfactant and surfactant inhibitors in meconium aspiration syndrome

Surfactant indices and inhibitors were measured in lung lavage fluid from 8 infants with meconium aspiration syndrome (MAS) who were receiving mechanical ventilation and 11 healthy control subjects. Surfactant phospholipid and surfactant protein A content in MAS was not different from that of control subjects, but concentrations of total protein, albumin, and membrane-derived phospholipid were elevated. All infants with MAS had hemorrhagic pulmonary edema. These findings reinforce the notion of MAS as a toxic pneumonitis with epithelial disruption and proteinaceous exudation. (J Pediatr 2001;138:113-5)

Myocardial stunning secondary to aneurysmal subarachnoid hemorrhage

Background Although subarachnoid hemorrhage (SAH) is often associated with electrocardiographic abnormalities, profound effects on cardiac performance are rare. CASE DESCRIPTION A 57-year-old woman who developed loss of consciousness, respiratory distress, severe hypotension, and left ventricular hypokinesis with minimal coronary artery disease is described. Despite normal appearance of the coronary arteries on angiography, left ventricle function was so severely depressed that she required intra-aortic balloon pump support for 24 hours. Mental status changes prompted a head computed tomographic (CT) scan, which showed severe SAH and an intraventricular hemorrhage (IVH). Cerebral angiography demonstrated a basilar apex aneurysm. An echocardiogram done on hospital day 6 was normal. A left frontal ventriculostomy catheter was placed. This was later changed to a lumbar subarachnoid (SA) drain. The patient underwent an orbito-zygomatic craniotomy and aneurysm clipping. Although several serious medical problems occurred during her hospitalization, at follow-up, her sole neurological impairment was a minimal and resolving oculomotor paresis. CONCLUSION This patient’s respiratory failure and severe hypotension were initially thought to be due to a chemical pneumonitis or a cardiomyopathy. However, her symptoms ultimately proved to be secondary to a ruptured basilar apex aneurysm. The complex relationship of SAH to myocardial stunning, as illustrated by this patient, is discussed.

Preoperative Anesthesia Clinic

WHAT IS A PREOPERATIVE ANESTHESIA CLINIC? preoperative means: before surgery anesthesia means: methods to put you asleep and/or make you pain-free for surgery anesthesia clinic means: a space within the hospital in which you can talk to an anesthesiologist and a nurse in the days before your surgery A preoperative anesthesia clinic Figure 1 Image 1: A preoperative anesthesia clinic Figure 2 WHY IS IT GOOD TO HAVE A PREOPERATIVE ANESTHESIA CLINIC? The goal of the preoperative anesthesia clinic is to clear the patient medically for anesthesia prior to having either surgery or another painful procedure. All patients must be cleared for anesthesia even if they are scheduled for sedation (combination of medications causing drowsiness) as complications during the procedure may require the patient to receive general anesthesia (patient being completely asleep). The objective is to determine whether the patient is optimized (best prepared) for surgery. That is, is the patient's health as good as it can be considering their medical history and prescribed medications. DO ALL HOSPITALS HAVE A PREOPERATIVE ANESTHESIA CLINIC? No, not all hospitals have such a clinic. In order to operate such a clinic a hospital must have enough space, personnel and money. It is not cheap to run a preoperative HOW DOES A TYPICAL VISIT LOOK? The appointment may consist of the following five parts: Preoperative Anesthesia Clinic 2 of 7 A Questionnaire filled out by the patient 1. Nurse's Interview 2. Anesthesiologist's Interview and Physical Exam 3. Tests: Laboratory (blood), Chest X ray, 4. Electrocardiogram (EKG); Possibly: Pulmonary Function Tests (lung), Cardiac stress test (heart), or other heart tests Summary Interview: Questions answered by doctor 5. and instructions given by nurse for admission WHAT KIND OF PAPERWORK WILL YOU HAVE TO FILL OUT? Patients will usually be asked to fill out a questionnaire describing their past medical history, current complaints, current medications, and other important information. A variety of questions are asked to gather information about the major organ systems, i.e. do you have chest pain, do you have difficulties do breathe, do you have known allergies, and so on. In addition, some questions about your social background are asked. And finally, some information about your insurance is collected. WHAT WILL YOU BE ASKED BY THE NURSE DURING YOUR VISIT? Two systems that Anesthesiologists focus on are the heart (cardiac) and the lung (respiratory) systems. If the patient has other existing diseases, these too are evaluated. Occasionally, an additional test may be used to evaluate current, new problems that may have arisen. After the paperwork is completed, the nurse will assess the patient's vital signs (blood pressure, heart rate, and temperature). If available from other hospital or doctor visits, it is extremely helpful for the patient to have a file containing their latest blood results, chest X ray report, electrocardiogram report, and other more specialized reports such as cardiac stress test, heart electrocardiogram and/or echocardiogram, CT scan reports, or pathology reports. We usually gather these documents by fax from the respective doctors' offices during your visit but this may cause a significant delay in the time spent in the preoperative anesthesia clinic. Figure 3 Image 2: A nurse interview WHAT WILL YOU BE ASKED BY THE DOCTOR (ANESTHESIOLOGIST) DURING YOUR VISIT? The anesthesiologist will start by reviewing the available information in the medical chart of the patient. The anesthesiologist will typically fill out a preoperative evaluation sheet that will be used to prepare the best plan for anesthesia. Medications are discussed in detail. Having a pre prepared list of doses of medications can be extremely helpful for the medical staff. Which medications to be taken prior to the procedure will be outlined during the visit. Patients are instructed to not eat or drink anything after midnight the night prior to the surgery or procedure. Eating or drinking will result in cancellation of the planned procedure that day. If the patients have food in their stomach they may inadvertently vomit it into the lungs during their anesthesia which can result in a chemical pneumonia (aspiration pneumonia). This could result in being put on the lung machine (ventilator) in the intensive care unit (ICU) and might lead to deadly complications. Preoperative Anesthesia Clinic 3 of 7 Figure 4 Images 3 and 4: The “Anesthesiologist” flag indicates that the patient is ready to be seen by an anesthesiologist; An anesthesiologist interview

Inhibitory effect of meconium on pulmonary surfactant function tested in vitro using the stable microbubble test

Meconium aspiration syndrome is related to mechanical obstruction of the airways and subsequent chemical pneumonitis. It has also been suggested that meconium causes inhibition of surfactant function. To assess its inhibitory effect on surfactant function in vitro, we used a stable microbubble (SM) test that was thought to reflect the adequacy of pulmonary surfactant. The mixtures were prepared by adding serial dilutions of human meconium to various concentrations of Surfactant-TA (Surfacten). The SM count at each concentration of surfactant significantly increased with the increasing concentration of surfactant. This shows that the SM test closely reflects the quantified function of surfactant. When various concentrations of meconium were added to the surfactant concentration of 0.05 mg/ml and 0.25 mg/ml, the SM test results were decreased even at low concentrations of meconium. Also the increase in the meconium concentration caused a decrease in the SM test result, which was dependent on the surfactant and the meconium concentration, accordingly. These results suggest that meconium inhibits surfactant function. The stable microbubble test is an effective indirect method that tests the changes in surfactant quantity. In the in vitro experiment, we observed an inhibitory effect of meconium on the surfactant activity using the stable microbubble test.

Inorganic dust pneumonias: the metal-related parenchymal disorders.

In recent years the greatest progress in our understanding of pneumoconioses, other than those produced by asbestos, silica, and coal, has been in the arena of metal-induced parenchymal lung disorders. Inhalation of metal dusts and fumes can induce a wide range of lung pathology, including airways disorders, cancer, and parenchymal diseases. The emphasis of this update is on parenchymal diseases caused by metal inhalation, including granulomatous disease, giant cell interstitial pneumonitis, chemical pneumonitis, and interstitial fibrosis, among others. The clinical characteristics, epidemiology, and pathogenesis of disorders arising from exposure to aluminum, beryllium, cadmium, cobalt, copper, iron, mercury, and nickel are presented in detail. Metal fume fever, an inhalation fever syndrome attributed to exposure to a number of metals, is also discussed. Advances in our knowledge of antigen-specific immunologic reactions in the lung are particularly evident in disorders secondary to beryllium and nickel exposure, where immunologic mechanisms have been well characterized. For example, current evidence suggests that beryllium acts as an antigen, or hapten, and is presented by antigen-presenting cells to CD4+ T cells, which possess specific surface antigen receptors. Other metals such as cadmium and mercury induce nonspecific damage, probably by initiating production of reactive oxygen species. Additionally, genetic susceptibility markers associated with increased risk have been identified in some metal-related diseases such as chronic beryllium disease and hard metal disease. Future research needs include development of biologic markers of metal-induced immunologic disease, detailed characterization of human exposure, examination of gene alleles that might confer risk, and association of exposure data with that of genetic susceptibility.

Aerodigestive foreign bodies

Accidents with foreign bodies (FBs) are most common within the first two years of life. The airway FBs present a diagnostic dilemma as both the history and the investigations can be misleading. The persistent hypoxia presents a threat to life as does extraction. Moreover, the chemical pneumonitis induced by vegetative FB makes the situation even more worse. The FB of digestive tract are comparatively benign unless long standing. It is neither necessary for the airway FB to present with respiratory symptoms and signs nor for the FB of digestive tract to complain of dysphagia/throat pain. Oesophagoscopy may have to be done if an esophageal FB is causing only recurrent respiratory infections without dysphagia. The situation in dealing with FB varies from site to site in the aerodigestive tract. This article stresses the various dubious factors including the history, examination and investigation which can lead to misdiagnosis and also those problems which are encountered during planned extraction as well as post-operatively.

Review article: acute inorganic mercury vapor inhalation poisoning.

Mercury contamination is a serious environmental problem worldwide. Two primary sources of contamination are dumping of large quantities of inorganic mercury and exposure in the mining industry. Although the actual fatal level of mercury vapor is not known, exposure to more than 1-2 mg/m3 of elemental mercury vapor (Hg0) for a few hours causes acute chemical bronchiolitis and pneumonitis. Two hours after exposure, lung injury appears as hyaline membrane formation, and finally, extensive pulmonary fibrosis occurs. Clinical findings correlate with the duration of exposure, the concentration of mercury, and the survival time after exposure. There is no correlation between pathological findings and the concentration of mercury in the tissues. Necrosis of proximal convoluted tubules may be attributed to the disruption of the enzyme systems of Hg2+-sulfhydryl compounds. Metallothionein protein (MT), induced by the accumulation of Hg2+ in the kidneys, may play an important role in detoxication after it forms a non-toxic Hg2+-MT compound. Despite the deposition of mercury in the brain, compared with organic mercury, inorganic mercury did not seem to damage the neurons. Drugs such as chelating agents and corticosteroids appear to effectively decrease the inflammation and delay pulmonary fibrosis.

A Case of Chemical Pneumonitis Induced by Ingestion of Hydrocarbon

A 33-year-old woman was presented with dyspnea and chest discomfort after indigesting approximately 500ml of oil paint brush washing fluid. Hypoxic symptoms and radiographic infiltrates rapidly progressed. The patient was intubated and received mechanical ventilation. Bronchoalveolar lavage and transbronchial lung biopsies were performed. The CT scan of the lung showed bilateral extensive pneumonitis with necrosis and the lung tissue pathologic findings showed diffuse alveolar damage with extensive necrosis and numerous lipidladen macrophages. After intensive medical care with mechanical ventilation, her symptoms and radiological findings improved.

Pneumomediastinum Associated with Inhalation of White Smoke

Hexachloroethane (HC) smoke, also known as white smoke, is an obscurant used in numerous military situations. Many adverse health effects are associated with the use of white smoke, some of which are potentially life threatening. Inhalation is the most frequent route of injury. Two deaths among U.S. Army personnel resulted from HC smoke exposure in 1988. As recently as 1997, a United Nations soldier in Bosnia died after an HC smoke canister was discharged in his tent. Injuries are predominantly pulmonary and range from cough and dyspnea to chemical pneumonitis, pulmonary edema, and adult respiratory distress syndrome. In the case presented, a soldier developed pneumomediastinum after exposure to HC smoke. This is the first case reported in the literature of pneumomediastinum associated with HC smoke inhalation.

Fungal spores: hazardous to health?

Fungi have long been known to affect human well being in various ways, including disease of essential crop plants, decay of stored foods with possible concomitant production of mycotoxins, superficial and systemic infection of human tissues, and disease associated with immune stimulation such as hypersensitivity pneumonitis and toxic pneumonitis. The spores of a large number of important fungi are less than 5 microm aerodynamic diameter, and therefore are able to enter the lungs. They also may contain significant amounts of mycotoxins. Diseases associated with inhalation of fungal spores include toxic pneumonitis, hypersensitivity pneumonitis, tremors, chronic fatigue syndrome, kidney failure, and cancer.

Zinc.

The use of zinc in metal alloys and medicinal lotions dates back before the time of Christ. Currently, most of the commercial production of zinc involves the galvanizing of iron and the manufacture of brass. Some studies support the use of zinc gluconate lozenges to treat the common cold, but there are insufficient data at this time to recommend the routine use of these lozenges. Zinc is an essential co-factor in a variety of cellular processes including DNA synthesis, behavioral responses, reproduction, bone formation, growth, and wound healing. Zinc is a relatively common metal with an average concentration of 50 mg/kg soil and a range of 10-300 mg/kg soil. Meat, seafood, dairy products, nuts, legumes, and whole grains contain relatively high concentrations of zinc. The mobility of zinc in anaerobic environments is poor and therefore severe zinc contamination occurs primarily near points sources of zinc release. The recommended daily allowance for adults is 15 mg zinc. The ingestion of 1-2 g zinc sulfate produces emesis. Zinc compounds can produce irritation and corrosion of the gastrointestinal tract, along with acute renal tubular necrosis and interstitial nephritis. Inhalation of high concentrations of zinc chloride from smoke bombs detonated in closed spaces may cause chemical pneumonitis and adult respiratory distress syndrome. In the occupational setting inhalation of fumes from zinc oxide is the most common cause of metal fume fever (fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, salivation). Zinc compounds are not suspected carcinogens. Treatment of zinc toxicity is supportive. Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) is the chelator of choice based on case reports that demonstrate normalization of zinc concentrations, but there are few clinical data to confirm the efficacy of this agent.

Herbicide (Roundup) Pneumonitis

A case of acute intoxication presented as toxic pneumonitis after exposure to Roundup (glyphosate) (Solaris Group, Monsanto; San Ramon, CA) herbicide in an agriculture worker. The correct etiologic factor causing this specific clinical picture was identified only 2 weeks later, after a thorough occupational history was taken and meticulous delineation of the working conditions and exposures of the involved worker were made. As a rule, occupational related diseases are not readily elucidated by nonoccupational physicians. However, most acute intoxication events are first encountered by such physicians. In these situations, rapid and comprehensive evaluation is necessary in order to clearly identify the causative agent(s) and to initiate the appropriate treatment. Consulting occupational physicians at this early stage may facilitate early and accurate diagnosis.

Many faces of pulmonary aspergillosis.

Aspergillus is a ubiquitous fungus. It is commonly isolated as an upper respiratory tract saprophyte and is the most frequent contaminant in laboratory specimens. Because species of aspergillus are omnipresent, one must be cautious in ascribing a causal role to the fungus obtained from patients. Aspergillus has low pathogenicity for humans and animals and rarely invades the immunologically competent host. Although the fungus can affect any organ system, the respiratory tract is involved in >90% of afflicted patients. Pulmonary aspergillosis, depending whether the host is atopic or immunosuppressed, may be classified under four categories: allergic or hypersensitivity syndromes, saprophytic colonization, invasive (infective) dissemination, and chemical or toxic pneumonitis. These entities differ clinically, radiologically, immunologically, and in their response to various therapeutic agents. An increased awareness, an aggressive approach to securing the diagnosis, and instituting early and appropriate therapy are needed to reduce the high morbidity and mortality caused by many of the aspergillus-related syndromes.

Morphology and function of pulmonary surfactant inhibited by meconium.

The pathophysiology of neonatal meconium aspiration syndrome (MAS) is related to mechanical obstruction of the airways and to chemical pneumonitis. It has also been suggested that meconium causes inhibition of surfactant function. To assess its in vitro effect on surfactant function and morphology, we used a pulsating bubble surfactometer to measure the dynamic surface tension of meconium-surfactant mixtures and observed their electron microscopic structures. The mixtures were prepared by adding serial dilutions of human meconium to various concentrations of Surfactant-TA (Surfacten) that had been used for the prevention and treatment of neonatal respiratory distress syndrome. Inhibition of the surface tension-lowering properties of Surfactant-TA was caused by the addition of meconium and depended on the concentration of the surfactant; the inhibition could be overcome by increasing the surfactant concentration. When meconium was added to Surfactant-TA, the characteristic ultrastructural features of the latter, the loosely stacked layers, changed to a spherical lamellar structure and folded linear structures. These results suggest that meconium inhibits surfactant function by altering surfactant morphology. Our morphologic and functional findings support the new concept that surfactant inhibition may play a role in the pathophysiology of MAS.

薬剤性肺炎の最近の動向と問題点

薬剤性肺炎の最近の動向と問題点

Direct Administration of Charcoal Into the Lung and Pleural Cavity

We report the inadvertent administration of activated charcoal in water into the right lung and pleural cavity of a 51-year-old man being treated for a salicylate overdose. A mild chemical pneumonitis developed, as did a sterile empyema. Charcoal-stained fluid drained through a thoracostomy tube for 8 weeks. The patient was discharged in good condition but died 4 days later after taking another overdose. Direct administration of charcoal into the lungs is best prevented by radiographic confirmation of the location of the tube. Charcoal in water may cause less severe pulmonary injury than charcoal in sorbitol. [Sabga E, Dick A, Lertzman M, Tenenbein M: Direct administration of charcoal into the lung and pleural cavity. Ann Emerg Med November 1997;30:695-697.]