New Post has been published on Preventive measures in Asthma
New Post has been published on http://the-asthma.com/details-about-chronic-asthma-due-to-toluene-diisocyanate.html
Details about Chronic Asthma Due to Toluene Diisocyanate
Toluene diisocyanate (TDI) is an important cause of occupational respiratory disease with approximately 5 percent of exposed workers developing occupational asthma in industries using TDI. There is uncertainty regarding the long-term prognosis of workers with TDI asthma once they are removed from isocyanate exposure. Recovery of asthma after removal from isocyanate exposure has been reported; however, there are reports documenting airway flow abnormalities for days to weeks after occupational exposure or bronchial challenge to TDI in sensitized individuals. Other clinical studies suggested respiratory symptoms following isocyanate exposure persist for extended periods, but TDI sensitivity was not documented in these cases by inhalation challenge testing. Since clinical history alone may be nondiscriminatory and no in vitro test has sufficient diagnostic sensitivity or specificity, controlled bronchial challenge testing remains the only way to confirm hypersensitivity to TDI. The present report reviews our experience with 12 isocyanate workers who had been removed from their occupational exposure to TDI and who were studied with a TDI inhalation challenge test. A retrospective review of the characteristics of these workers is presented in order to assess the course of their respiratory disease.
Patients were referred to the Occupational Health Clinic for evaluation of possible TDI asthma over a five-year period from 1980 to 1985. In only 12 workers was the clinical and occupational history consistent with a diagnosis of occupational asthma due to TDI. Approximately 20 other subjects were evaluated, and the history was not consistent with a diagnosis of occupational asthma. Prevent asthma decline with ventolin. The 12 workers reported symptoms consistent with a diagnosis of TDI asthma including cough, shortness of breath, and wheezing which occurred for the first time while working with isocyanates. These symptoms worsened with continued TDI exposure and improved when the workers were completely removed from isocyanate exposure. Three workers reported significant nocturnal asthma symptoms; chest pain was a prominent symptom in one subject (4). The ages of these 12 workers ranged from 18 to 61 years and included ten men and two women. Three workers (4, 8, and 11) were current cigarette smokers; three subjects were past cigarette smokers (1, 4, and 6). There was no personal nor family history of asthma, hayfever, or other allergies prior to the onset of symptoms in ten of the 12 subjects.
Exposure to TDI was substantiated through their employers records. The workers held a wide variety of jobs which required different levels of skills, education, and training, but their exposure to TDI could be classified into three categories. Five individuals performed assembly line work with exposure to TDI used in a polyurethane foam injection process. Four workers were involved in spray painting polyurethane paints containing TDI, and three workers were exposed to TDI spills, often as a member of the cleanup crew.
Eight of these 12 workers reported persistent respiratory symptoms which required daily β-agonist bronchodilators and/or aminophylline despite leaving their occupational exposure to isocyanates. In several cases, intermittent steroids were used for past management of acute asthma during the course of their respiratory disease. No subject was receiving corticosteroids at the time of evaluation nor at any time up to four weeks before admission to the hospital. Buy asthma inhalers to get rid of asthma symptoms (for example: Advair Inhaler, Flovent Inhaler or Ventolin Inhalers)
On their initial evaluation, each worker received a physical examination, pulmonary function tests, and phlebotomy for determination of serum specific IgE to various isocyanate-protein conjugates. Three persons had evidence of mild airway obstruction, and one subject had moderate airway obstruction on their initial spirometric evaluation. The remaining individuals had normal pulmonary function test results when first seen in our clinic.
All patients were admitted to the University of Cincinnati General Clinical Research Center. Informed consent was obtained from each. The following protocol was used: day 1, history and physical exam, methacholine challenge; day 2, saline aerosol control challenge; day 3, low dose TDI challenge (10 ppb, 10 minutes); day 4, high dose TDI challenge (20 ppb, 20 minutes); and day 5, discharge. All medications not needed by the subjects were discontinued 48 hours prior to the TDI challenges. Inhaled isoetharine or metaproterenol was used if needed for control of respiratory symptoms. Theophylline and corticosteroids were not used on the bronchial challenge days unless needed to treat significant bronchospasm.
Pulmonary function tests were performed according to criteria established by the American Thoracic Society using a precalibrated Ohio Medical Company dry-rolling spirometer connected to a microprocessor. Measurement of FEV1, FVC, and flow rates were made in triplicate. The best value was chosen for analysis.
Inhalation Challenge to TDI
Inhalation challenge studies to TDI were performed using a specially designed inhalation facility for this purpose. The TDI vapors were generated by passing dry filtered air over the liquid surface of 99.6 percent 2,4-TDI. The TDI air stream leaving the generation system was diluted with another source of fresh filtered air at the chamber inlet. Different concentrations of TDI were generated by adjusting the various airflow rates. The air TDI-mixture passed into a 271 L inhalation chamber through which the patient breathed via a mouthpiece attached to the chamber. The concentration of TDI at a port next to the mouthpiece was continuously monitored by a rapid reading isocyanate recorder during and following TDI inhalation challenges. Periodic verification of TDI levels were made using the Marcali method. Serial pulmonary function tests were performed throughout day 2,3, and 4 of the study at time 10, 20, 30, 40, 60 minutes, hourly for six hours, and at 12 and 24 hours following the inhalation challenges. A positive challenge test was defined as a 20 percent fall in FEV1. No further testing was performed following a positive response to the low dose TDI challenge.
Bronchial Challenge to Detect Airways Hyperreactivity
In the majority of subjects, methacholine challenge tests were performed using a Collison nebulizer which delivered 11.94 μg methacholine per second (airflow rate 12.5 L/minute at 26 PSI; aerosol mass median aerodynamic diameter 1.10 μl with geometric standard deviation of 2.20 μ. The cumulative inspiratory time was measured using a Fairchild pressure sensor in combination with a Lafayette stop clock. Cumulative inspiratory dose of methacholine (in micrograms) delivered to the respiratory system was calculated from the cumulative inspiratory time and the known rate of methacholine delivery. The rate of breathing was controlled by coaching the patients to inspire for 5 to 6 seconds for each breath. The aerosol was inhaled via a disposable mouthpiece connected to a one-way Hans Rudolph valve.
Following baseline spirometry, the patient was given a 30-second isotonic saline challenge followed by repeat spirometry two minutes after challenge. Providing there is no reaction to saline, the first dose of methacholine is then given (usually 100 to 200 μg) followed by pulmonary function tests two minutes after exposure. A test is considered positive when there is a 20 percent or greater fall in FEV1s otherwise additional methacholine is administered until a total cumulative dose of 2,000 μg is given. Hie provocative dose corresponding to a 20 percent fall in FEV1 (PD,) is calculated by performing a linear regression of the log transformation of dose vs percentage fall in FEV1( Experience in our laboratory has shown that nearly all asthmatic patients respond to less than 2,000 μg methacholine using our generation system. Similar results have been reported by other investigators. In two subjects, a different method was employed. Five inhalations of increasing doses (2 mg/ml-25 mg/ ml) of methacholine were used until a 20 percent fall in FEV1 was reached.
A cold air challenge to assess the degree of nonspecific airway reactivity was performed in one subject according to a reported protocol. Briefly, a patient undergoes eucapnic hyperventilation with cold air (—40°C) for six minutes. A positive cold air challenge is defined as a 9 percent decrease in FEV1 when measured five and ten minutes postchallenge compared to a prechallenge FEVj measurement.
A RAST procedure using methylcellulose discs coupled with TDI-HSA, PTI-HSA, MDI-HSA, and HDI-HSA was performed as previously described. A positive result was defined as percentage of binding two times that of laboratory workers with no known exposure to isocyanates.