Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of airway hyperresponsiveness (AHR), a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM is unknown. The current study examined the hypothesis that relaxation induced by PACAP is reduced in bronchial smooth muscle (BSM) of allergic asthma. The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated. Tension study showed a BSM hyperresponsiveness to acetylcholine in the OA-challenged mice. Both quantitative RT-PCR and immunoblot analyses revealed a significant decrease in PAC1 receptor expression in BSMs of the diseased mice. Accordingly, in the antigen-challenged group, the PACAP-induced PAC1 receptor-mediated BSM relaxation was significantly attenuated, whereas the relaxation induced by vasoactive intestinal polypeptide was not changed. These findings suggest that the relaxation induced by PACAP is impaired in BSMs of experimental asthma due to a downregulation of its binding partner PAC1 receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

Identification of late asthmatic reactions following specific inhalation challenge

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based.ObjectivesTo identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days.MethodsFifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI.Results45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma.ConclusionThe pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

Cutaneous sensitization to aziridine preceding the onset of occupational asthma

We describe a 47-year-old non-atopic woman, working as a spray painter in a tannery for 23 years, with a 16-year history of cutaneous symptoms and a subsequent 2-year history of asthmatic symptoms after exposure to aerosol and vapour of polyfunctional aziridine (PFA) at work. To confirm the occupational origin of the dermatitis and asthma we performed a skin prick test with PFA and a specific inhalation challenge (SIC) with PFA. Prick test with PFA elicited an immediate positive skin reaction. She developed an immediate asthmatic reaction upon SIC with PFA. The onset of occupational dermatitis before asthma is consistent with the hypothesis that the sensitization to PFA was triggered in the skin. The observation that the reactions elicited in skin and airways upon exposure to PFA exhibited the same time course, suggests a similar mechanism at both sites. Thus, the avoidance of both skin and airway exposure to PFA should be recommended in workplace hygiene practice.

Occupational Asthma in Antibiotic Manufacturing Workers: Case Reports and Systematic Review

Background. The risks of occupational asthma (OA) from antibiotics are uncertain. We report 4 new cases and a systematic review of the literature. Methods. Cases were identified through a specialist clinic, each underwent specific provocation testing (SPT). We subsequently reviewed the published literature. Results. The patients were employed in the manufacture of antibiotics; penicillins were implicated in three cases, in the fourth erythromycin, not previously reported to cause OA. In two, there was evidence of specific IgE sensitisation. At SPT each developed a late asthmatic reaction and increased bronchial hyperresponsiveness. 36 case reports have been previously published, 26 (citing penicillins or cephalosporins). Seven cross-sectional workplace-based surveys found prevalences of 5–8%. Conclusions. OA in antibiotic manufacturers may be more common than is generally recognised. Its pathogenesis remains unclear; immunological tests are of uncertain value and potential cases require confirmation with SPT. Further study of its frequency, mechanisms, and diagnosis is required.

A whey-based glutathione-enhancing diet decreases allergen-induced airway contraction in a guinea-pig model of asthma

Since an allergen-induced early asthmatic reaction is likely to be accompanied by oxidative stress and since levels of the endogenous antioxidant glutathione can be enhanced by a whey-based diet (undenatured whey protein concentrate, UWPC), it was investigated whether UWPC could alleviate allergen-induced lung contractions. Guinea pigs were fed water or UWPC twice a day starting at day − 3 up to day 20. The animals were sensitised to ovalbumin or received saline on day 0. Serum samples were taken at several days after sensitisation to measure allergen-specific IgG. On day 20, lungs were isolated and perfused with buffer containing the allergen ovalbumin. Airway contractions were assessed, and mediators and indicators for oxidative stress were measured in the lung effluent. Moreover, glutathione levels were determined in the liver. The indicator of oxidative stress and airway contractile mediator, 8-iso-PGF2α, was increased upon ovalbumin challenge in ovalbumin-sensitised groups. Furthermore, thiobarbituric acid-reactive substances (TBARS) were increased as well. Sensitisation with ovalbumin increased IgG levels from day 12 up to day 20, which were not influenced by the UWPC diet. In contrast, the UWPC diet significantly enhanced glutathione levels in the liver. Moreover, the UWPC diet significantly reduced the ovalbumin-induced anaphylactic response by 45 % and decreased PGE2 levels by 55 % in the effluent fluid. We show for the first time that during anaphylaxis, there is acute oxidative stress in the respiratory tract. The UWPC diet did not influence the sensitisation response to the allergen but did increase endogenous glutathione levels. The UWPC diet profoundly reduces allergen-induced airway constrictions, which opens new avenues for dietary management of allergic diseases.

Occupational allergy to Limonium sinuatum — a case report

Decorative flowers are known to be a cause of occupational allergy in the floral industry. The allergic manifestations induced by flowers include asthma, rhinoconjunctivitis and urticaria. We present a case of a 55-year-old woman, who has been working for the last 30 years as a gardener with various kinds of flowers, e.g., Limonium sinuatum (LS), chrysanthemum, sweet William (Dianthus barbatus) and Lilium. During the last 10 years she has developed nasal and eyes symptoms, dry cough, dyspnoea, chest tightness and wheezing. Clinical examination, routine laboratory testing, chest radiography, skin prick tests (SPT) involving common allergens, native plants pollens and leaves by the prick-prick technique, rest spirometry, methacholine challenge test and specific inhalation challenge test (SICT) were conducted. SPT results to common allergens were positive for grass pollens. SPT with native plants pollens and leaves showed a positive reaction only for LS. SICT induced an isolated early asthmatic reaction and significant increase in the number of eosinophils in the nasal lavage fluid. Additionally, significant increase in non-specific bronchial hyperreactivity was observed after SICT. To our knowledge, the presently described report is the first one of Limonium sinuatum induced occupational asthma and rhinitis in a Polish gardener.

Outcome of Occupational Asthma after Removal from Exposure: A Follow-Up Study

BACKGROUND: Despite being removed from their workplace, the majority of workers with occupational asthma (OA) remain afflicted with asthma.OBJECTIVES: To assess the time course of clinical, functional and inflammatory parameters in subjects with OA over a four-year period, and whether the airway inflammation observed at the time of the diagnosis predicts the outcome of OA.METHODS: The present study was a four-year, prospective, longitudinal investigation of workers with OA. Spirometry, methacholine challenge and sputum induction were performed at two weeks, and followed up at six months, and one, two, three and four years after the performance of specific inhalation challenges.RESULTS: A total of 24 subjects were enrolled. Overall, clinical and functional characteristics remained stable during the four-year follow-up period. Sputum eosinophil (Eos) counts decreased within two weeks after exposure. Two groups of subjects were identified according to low (less than 2%, Eos−) or high (2% or greater, Eos+) Eos counts after exposure to the offending agent. The Eos+ group decreased their dose of inhaled corticosteroids, had a trend toward an improvement of airway responsiveness as well as a stable forced expiratory volume in 1 s (FEV1), whereas the Eos− group showed a decrease in FEV1, without any improvement in their functional parameters. The Eos− group also had an increase in sputum neutrophils after exposure to the occupational agents as well as during the follow-up period.CONCLUSION: There was a rapid decrease in eosinophilic inflammation after removal from exposure. Subjects with a noneosinophilic asthmatic reaction during specific inhalation challenge seemed to have a poorer prognosis than subjects with eosinophilic airway inflammation.