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Exposure to fine particulate matter (PM 2.5 ) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM 2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights. Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM 2.5 . Exposure to PM 2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM 2.5 exposure. PM 2.5 exposure (mean 433 ± 111 μg/m 3 in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system®. A parallel increase of pro-inflammatory cytokines (IL-6, IL-17, TNF-α and IFN-γ), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM 2.5 exposed animals. In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Asthma is a chronic respiratory disease which is susceptible to children and causes great harm to them. Recently, Interferon-related developmental regulator 1 (IFRD1) was proved to be participant in regulating lung diseases, and its abnormal expression was shown in pathological airway tissues. Our study aimed to demonstrate the role and modulatory mechanism of IFRD1 in the pathogenesis of asthma. First, we evaluated the expression of IFRD1 in the lungs of asthmatic patients. C57BL/6 mice and human bronchial epithelioid (HBE) cells were respectively induced by ovalbumin (OVA) and lipopolysaccharide (LPS) to construct asthma models in vivo and in vitro. Using adenovirus and pcDNA vectors, we carried out overexpression assays on mice and cell models. Additionally, the potential mechanism of IFRD1 on regulating asthma process was elucidated by targeting NF-κB pathway. The results showed that IFRD1 was significantly down-regulated in asthma lung tissues, as well as the in vivo and in vitro models of asthma. Besides, OVA induced the inflammation responses and hyperreactivity of airway in mice, and LPS also caused inflammatory cytokine secretion and apoptosis of HBE cells, while cell viability was inhibited. However, IFRD1 overexpression dramatically reversed the effects of OVA and LPS. We subsequently discovered that the NF-κB pathway was activated in asthmatic cells, and NF-κB signaling activation was involved in IFRD1 regulated asthma responses of HBE cells. In conclusion, our study indicated that IFRD1 inhibited the asthmatic responses of airway via the NF-κB pathway inactivation. The evidence presented herein might provide a novel sight for asthma therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Asthma is a chronic debilitating airway disease affecting millions of people worldwide. Although largely thought to be a disease of the first world, it is now clear that it is on the rise in many middle- and lower-income countries. The disease is complex, and its etiology is poorly understood, which explains failure of most treatment strategies. We know that in children, asthma is closely linked to poor lung function in the first 3-years of life, when the lung is still undergoing post-natal alveolarization phase. Epidemiological studies also suggest that environmental factors around that age do play a critical part in the establishment of early wheezing which persists until adulthood. Some of the factors that contribute to early development of asthma in children in Western world are clear, however, in low- to middle-income countries this is likely to differ significantly. The contribution of fungal species in the development of allergic diseases is known in adults and in experimental models. However, it is unclear whether early exposure during perinatal or post-natal lung development influences a protective or promotes allergic asthma. Host immune cells and responses will play a crucial part in early development of allergic asthma. How immune cells and their receptors may recognize fungi and promote allergic asthma or protect by tolerance among other immune mechanisms is not fully understood in this early lung development stage. The aim of this review is to discuss what fungal species are present during early exposure as well as their contribution to the development of allergic responses. We also discuss how the host has evolved to promote tolerance to limit hyper-responsiveness to innocuous fungi, and how host evasion by fungi during early development consequentially results in allergic diseases., (Copyright © 2019 Hadebe and Brombacher.)

The incidence and severity of asthma preponderate in women versus men. Leukotrienes (LTs) are lipid mediators involved in asthma pathogenesis, and sex disparities in LT biosynthesis and anti-LT pharmacology in inflammation have recently emerged. Here, we report on sex dimorphism in LT production during allergen sensitization and its correlation to lung function. While high plasma levels of IgE, as sensitization index, were elevated in both sexes, LT levels increased only in lungs of female ovalbumin-sensitized BALB/c mice. Sex-dependent elevated LT levels strictly correlated to an enhanced airway hyperreactivity, pulmonary inflammation and mast cell infiltration/activation in female mice. Importantly, this sex bias was coupled to superior therapeutic efficacy of different types of clinically used LT modifiers like zileuton, MK886 and montelukast in female animals. Our findings reveal sex-dependent LT production as a basic mechanism of sex dimorphism in allergic asthma, and suggest that women might benefit more from anti-LT asthma therapy., (Copyright © 2018. Published by Elsevier Ltd.)

Background: As asthma-like symptoms are common in CF, we evaluated reversible airway obstruction and associated characteristics., Methods: Retrospective analysis of charts including spirometry and bronchodilator response., Results: Of 190 CF patients (103 at Schneider's, 87 at Hadassah), aged 14.4 (4-76) years, median (range), 39% had reversible obstruction (ΔFEV1% predicted ≥12%), associated with younger age (p=0.01) and severe genotype (p=0.02). There was no association with family history of asthma, serum IgE, blood eosinophils, pancreatic status, FEV1<40% predicted, Aspergillus or pseudomonas infection. Of patients with reversible obstruction, 74% were on bronchodilator and 68% on inhaled corticosteroid therapy but 54% and 57% respectively receiving these therapies did not have reversible obstruction., Conclusions: Reversible airway obstruction is common in CF, more frequent in younger patients and with severe genotype, with no correlation to markers of atopy or CF clinical severity. Bronchodilator and inhaled corticosteroid therapies are commonly prescribed even without reversible obstruction., (Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Asthma is a chronic inflammatory disorder of the airway. It is characterized by airway hyper-reactivity, which can be attributed to the chronically inflamed airway. However, the molecular mechanism is still under investigation. In this article, we have shown that IL-1β is a key molecule that can orchestrate both Toll-like receptor and muscarinic receptor pathways, and that antagonizing the function of IL-1β has a promising future as a potential drug target for asthma treatment. IL-1β can activate NF-κB pathways via Toll-like receptors, and NF-κB will eventually transactivate the genes of cytokines, chemokines, proteins of the complement system, adhesion molecules and immune receptors involved in inflammation. IL-1β can activate eosinophils, which can release major basic protein (MBP) to antagonize the M2 receptors leading to excessive acetylcholine release. Acetylcholine has an effect on M3 receptors, which are related to airway smooth muscle contraction and mucus production. IL-1β is reported to activate COX-2 resulting in heterologous desensitization of adenylate cyclase and impairs relaxation of the ASM. IL-1β is involved in mediation of neutrophilic inflammation. Identification of the prominent role of IL-1β in asthma could lead to successful use of anti-IL1β agents.

Background: This study presents an animal model of native airway hyperresponsiveness (AHR). AHR is a fundamental aspect of asthma and reflects an abnormal response characterized by airway narrowing following exposure to a wide variety of non-immunological stimuli. Undescended testis (UDT) is one of the most common male congenital anomalies. The orl rat is a Long Evans substrain with inherited UDT. Since boys born with congenital UDT are more likely to manifest asthma symptoms, the main aim of this study was to investigate the alternative hypothesis that orl rats have greater AHR to a methacholine aerosol challenge than wild type rats., Methods: Long Evans wild type (n = 9) and orl (n = 13) rats were anesthetized, tracheostomized, and mechanically ventilated at 4 weeks of age. Escalating concentrations of inhaled methacholine were delivered. The methacholine potency and efficacy in the strains were measured. Respiratory resistance was the primary endpoint. After the final methacholine aerosol challenge, the short-acting β2-adrenoceptor agonist albuterol was administered as an aerosol and lung/diaphragm tissues were assayed for interleukin (IL)-4, IL-6, and tumor necrosis factor (TNF)-α. Histological and histomorphometrical analyses were performed., Results: The methacholine concentration-response curve in the orl group indicated increased sensitivity, hyperreactivity, and exaggerated maximal response in comparison with the wild type group, indicating that orl rats had abnormally greater AHR responses to methacholine. Histological findings in orl rats showed the presence of eosinophils, unlike wild type rats. β2-Adrenoceptor agonist intervention resulted in up-regulation of IL-4 diaphragmatic levels and down-regulation of IL-4 and IL-6 in the lungs of orl rats., Conclusion: orl rats had greater AHR than wild type rats during methacholine challenge, with higher IL-4 levels in diaphragmatic tissue homogenates. Positive immunostaining for IL-4 was detected in lung and diaphragmatic tissue in both strains. This model offers advantages over other pre-clinical murine models for studying potential mechanistic links between cryptorchidism and asthma. This animal model may be useful for further testing of compounds/therapeutics options for treating AHR., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Epidemiologic studies suggest that increased concentrations of airborne spores of Aspergillus fumigatus closely relate to asthma aggravation. Chronic exposure to A. fumigatus aggravates airway inflammation, remodeling, and airway hyperresponsiveness in asthmatic rats. The effects of chronic exposure to A. fumigatus on epidermal growth factor receptor (EGFR) expression in the airway epithelial cells of asthmatic rats remain unclear. This study aimed to investigate the effects of chronic exposure to A. fumigatus on injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression in the airway epithelial cells of asthmatic rats. A rat model of chronic asthma was established using ovalbumin (OVA) sensitization and challenge. Rats with chronic asthma were then exposed to long-term inhalation of spores of A. fumigatus, and the dynamic changes in injury and shedding of airway epithelium, goblet cell metaplasia, and EGFR expression were observed and analyzed. Chronic exposure to A. fumigatus could aggravate airway epithelial cell damage, upregulate the expression of EGFR and its ligands EGF and TGF-α, promote goblet cell metaplasia, and increase airway responsiveness in rats with asthma. Chronic exposure to A. fumigatus upregulates the expression of EGFR and its ligands in asthmatic rats. The EGFR pathway may play a role in asthma aggravation induced by exposure to A. fumigatus.

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Se realizó una revisión que abarca los aspectos más importantes de la fisiología y genética del gen de la sintasa del óxido nítrico 1 así como su participación en la patogénesis del asma. El asma es una enfermedad común y compleja, caracterizada por obstrucción de las vías aéreas, hiperreactividad bronquial y en muchos casos atopia. Su causa aún no esta bien definida, pero se conoce que está influenciada por factores genéticos y ambientales. Para tratar de esclarecer la fuente precisa de la enfermedad, se realizan análisis de genes candidatos y al nivel ambiental la influencia de los alergenos de ácaros y otros factores de riesgo en el desarrollo de asma. Dentro de los genes candidatos, el gen de la sintasa del óxido nítrico 1 ha cobrado gran interés por su amplio papel en la patogénesis del asma, porque actúa como un neurotransmisor y broncodilatador que provoca una hiperrespuesta en las vías aéreasA review of the most important aspects of physiology and genetics of type 1 nitric oxide synthase gene as well as its involvement in asthma pathogenesis was made. Asthma is a common and complex disease characterized by obstruction of airways, bronchial hyperreactivity and in many cases atopy. The fundamental cause of this disease is not yet well defined but it is known that genetic and environmental factors have their bearing on it. To clarify the exact origin of this disease, candidate genes, the influence of mite allergens at environmental level and other risk factors for asthma were all analyzed. Among candidate genes, type 1 nitric oxide synthase gene has aroused great interest due to its extensive role in asthma pathogenesis becuase it acts as a neurotransmitter and bronchodilator that provides hyperresponse in airways

Abstract: Adenosine participates to asthma physiopathology by signaling through more than just one receptor subtype. Defining the role of each receptor is complicated by evidence that often results obtained on rodents do not coincide with human studies, but what emerges is that an important condition to establish hyperresponsiveness to adenosine in any species of sensitized animals is the exposure to allergen; this feature appears to be very similar to the human situation, since allergic humans regularly undergo exposure to allergen. Furthermore, A2B in humans, but A3 receptor in rodents, would mediate, indirectly, the bronchoconstriction in response to adenosine and would play the main role in adenosine-induced airway inflammation and airway hyperreactivity. On the other hand, A1 receptor over-expressed on asthmatic airways would mediate a direct adenosine bronchoconstrictor effect. Antagonists and agonists to adenosine receptors have been considered as antiasthmatic drugs but often their development has been limited by unwanted effects. Preventing adenosine accumulation in airways should be considered as a novel promising antiasthmatic strategy. [Copyright &y& Elsevier]

Abstract: Airway hyperreactivity is characterized by increased responsiveness to bronchoconstrictor stimuli and it is hallmark of asthma. Adenosine is an ubiquitous signaling nucleoside resulting from ATP catabolism, whose extracellular levels increase following cellular damage or stress. Adenosine plays a role in asthma; asthmatics, but not normal subjects, present bronchoconstriction following inhalation of adenosine or of its precursor, adenosine-5′-monophosphate, most likely via adenosine A2B receptor on mast cells. However, the mechanism underling the increased airway smooth muscle sensitivity to adenosine in asthmatics remains to be elucidated. Early experimental studies suggested the involvement of A1 receptor; this hypothesis has been confirmed by more recent studies on guinea pigs and is corroborated by the finding of an increased adenosine A1 expression on asthmatic bronchial tissues. Brown Norway rats, the strain usually used to assess asthma models, develop hyperresponsiveness to adenosine 3h following allergen challenge, but not 24h thereafter, without involvement of A1 receptor. Here, we investigated the role of adenosine A1 receptor in sensitized Wistar rats showing airway hyperresponsiveness 24h following allergen challenge. We found that on bronchi of sensitized Wistar rats challenged with allergen there is an increased adenosine A1 receptor expression on smooth muscle that is responsible for hyperresponsiveness to adenosine and ovalbumin. [Copyright &y& Elsevier]

Background: Airway mucus hypersecretion is associated with increased morbidity and mortality in patients with asthma. Chronic Aspergillus fumigatus ( A. fumigatus) exposure leads to aggravation of airway inflammation and remodeling, including goblet cell hyperplasia (GCH) and mucus hypersecretion in a rat model of asthma. The effects of chronic A. fumigatus exposure on the expression of airway mucin 5AC (MUC5AC) are unknown. Methods: The rat model of chronic asthma was set up by systemic sensitization and repeated challenge to ovalbumin (OVA). The asthmatic rats were exposed to chronic intranasal inhalation of A. fumigatus spores. The changes of MUC5AC expression, the extent of GCH, and airway hyperreactivity (AHR) were measured after exposure to the fungus. Results and Conclusions: Chronic exposure to A. fumigatus upregulates the expression of MUC5AC, and induces GCH in the airways of asthma rats, and the remodeling changes of the airway epithelium was positively correlated with AHR. Upregulation of MUC5AC and induction of GCH may be mechanisms by which chronic A. fumigatus exposure promotes the progression of asthma. [ABSTRACT FROM AUTHOR]

Abstract: In the present study we investigated the lymphocytes infiltration and other parameters of allergic lung inflammation comparing mice submitted to acute suppression of nitric oxide synthesis with mice deficient in inducible nitric oxide synthase (NOS2−/−) gene. At weekly intervals C57Bl/6 mice, wild type and NOS2−/− were sensitized twice with ovalbumin-alumen and challenged twice with ovalbumin aerosol and lungs examined 24 h later. In wild type mice, treatment with nitric oxide synthase inhibitor, N ω-nitro-l-arginine-methyl-ester (l-NAME) or aminoguanidine (i.p., 30 min before each ovalbumin challenge) caused a significant decrease in bronchoalveolar lavage cell number: eosinophils (90%), lymphocytes NK1.1+ (70%), Tγδ+ (50%), CD4+ (55%), CD8+ (60%) and B220+ (65%). Both inhibitors abolished airway hyperreactivity and significantly reduced mucus secretion (l-NAME 64%; aminoguanidine 58%). Surprisingly, in NOS2−/− mice these parameters of allergic lung inflammation were not significantly different when compared with wild type mice. In addition, treatment of NOS2−/− mice with l-NAME or aminoguanidine did not affect these parameters. Thus, acute inhibition of NOS2 activity inhibits asthma-like responses but absence of NOS2 has no affect. [Copyright &y& Elsevier]

Airway hyperresponsiveness in asthmatics, which may result from inflammation or remodeling, is expressed as the concentration of methacholine that causes a 20% fall in FEV[sub 1] in the concentration-response curve (PC[sub 20]). A decrease in PC[sub 20] may be due to a steeper curve (hyperreactivity) and/or a curve shift to the left (hypersensitivity). Our purpose was to analyze the relation of airway sensitivity and reactivity to airway pathological changes. The PC[sub 6], as sensitivity parameter, and the slope between PC[sub 20] and PC[sub 40] as reactivity parameter, were calculated. Total and differential cell counts in the bronchoalveolar lavage fluid, and percentage of epithelial shedding, basement membrane thickness, and submucosal thickness on bronchial biopsy, were measured. The PC[sub 6] showed a correlation with the baseline FEV[sub 1]%. The slope was significantly correlated with the basement membrane thickness, and also demonstrated a strong association with submucosal thickness. The PC[sub 20] showed a correlation with the baseline FEV[sub 1]% and the degree of epithelial shedding. These results suggest that the airway sensitivity and reactivity measurements reflect the degree of airway caliber and remodeling, respectively. [ABSTRACT FROM AUTHOR]

The effects of silymarin on bronchoconstriction induced by antigen challenge and on post-antigen challenge hyperresponsiveness to substance P were evaluated in sensitized guinea-pigs. Silymarin significantly decreased the bronchoconstriction due to antigen administration in the early phase of the response. In contrast, the dose–response curve for substance P recorded 1 h after antigen challenge was not modified by pretreatment with silymarin. The influence of the flavonoid on hyperresponsiveness to histamine in propranolol- and PAF (platelet-activating factor)-treated animals was also assessed. Silymarin did not affect hyperresponsiveness to histamine induced by either propranolol or PAF although it had inhibitory activity on the bronchial contractile response to the autacoid. These results suggest that silymarin has a protective effect in the early phase of allergic asthma, an effect, which may be related to a negative influence of the flavonoid on bronchial responsiveness to histamine. [Copyright &y& Elsevier]

Background: A group of patients with asthma-like symptoms and sensitivity to chemical irritants has shown an increased cough sensitivity to inhaled capsaicin compared to patients with asthma and to healthy controls. The condition is called sensory hyperreactivity (SHR), and the patients often feel that they are socially handicapped because of the risk of exposure to chemical irritantsin daily life. Methods: Twenty-six patients with asthma-like symptoms after exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or demonstrable bronchial obstruction, were selected for a study of the response to a capsaicin test and measurement of quality of life by a general health profile (the Nottingham Health Profile [NHP]). We also investigated whether there was a correlation between quality of life and sensitivity to capsaicin. Results: The patients demonstrated a dose-dependent response to the capsaicin provocation, with coughing and respiratory and other symptoms, that significantly differed from 12 healthy controls. The health profile showed that patients with SHR had a significantly reduced quality of life compared to reference values, and there was a significant correlation between the health profile and sensitivity to capsaicin. Conclusions: Patients with asthma-like symptoms verified by the capsaicin inhalation test for sensory hyperreactivity have a poor quality of life. The correlation between quality of life and sensitivity to capsaicin objectively demonstrates the validity of this general health profile study. [ABSTRACT FROM AUTHOR]

Background: A group of patients with asthma-like symptoms and sensitivity to chemical irritants, but without bronchial obstruction, has been found among subjects referred for suspected asthma. They have no well-defined diagnosis, and no objective diagnostic method has previously been available. These patients are more sensitive to inhaled capsaicin than are patients with asthma or healthy controls. The aim was to study cough and other capsaicin-induced symptoms and to test the effect of a drug (lidocaine) that inhibits nerve transmission in sensory nerves. Methods: Twelve patients were provoked with three different concentrations of inhaled capsaicin solutions in a randomized, double-blind order. They all had asthma-like symptoms and were sensitive to chemical irritants, but had noIgE-mediated allergy or demonstrable bronchial obstruction. Before the provocations, the patients inhaled lidocaine or placebo (saline), also ina double-blind, randomized order. The results were expressed as the numberof coughs and scores of various symptoms. Results: The patients reacted in a dose-dependent way with cough, airway, and eye symptoms, which were significantly reduced after preinhalation of lidocaine. Conclusions: A drug that inhibits transmission in sensory nerves successfully blocked the number of coughs and other symptoms provoked by inhalation of capsaicin. This indicates that the mechanisms underlying chemical sensitivity in these patients may originate in the sensory nervous system, and we call this condition “sensory hyperreactivity”. [ABSTRACT FROM AUTHOR]

BackgroundThe physiological and pharmacological consequences of repeated aero-allergen challenge have not been previously characterized in conscious, sensitized guinea-pigs. ObjectivesThis study was undertaken to compare the effects of two anti-inflammatory compounds, dexamethasone and Ro 20–1724, on an acute and chronic airway inflammation, in terms of airway function, reactivity and leucocyte infiltration. MethodsSensitized guinea-pigs received eight saline or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type 4 PDE inhibitor, Ro 20–1724 (3 mgkg-1), or dexamethasone (1.5 mg/kg-1), 30 min before and 6 h after each challenge. Airway function of the conscious animal (sGaw) was monitored over the duration of the first and final OvA challenge. Airway reactivity to the thromboxane mimetic, U46619, was also determined following the final OvA exposure as was the leucocyte infiltration. ResultsThe first antigen challenge induced a large early (0–3 h) and smaller late (17–24 h) bronchoconstrictor response. Neither phase was affected by the drug treatments. The final OvA challenge induced early and late phase bronchoconstrictor responses but of similar magnitude. The late phase was also significantly prolonged. Ro 20–1724 and dexamethasone significantly attenuated both phases. Airway reactivity to the inhaled thromboxane-mimetic, U46619, was also significantly enhanced at 120 h after the final OvA exposure in contrast to the saline challenged group. This hyperreactivity was attenuated by Ro 20–1724 and dexamethasone. Bronchoalveolar lavage after repeated OvA exposures revealed eosinophilia which was attenuated by Ro 20–1724 and dexamethasone. ConclusionsThis model demonstrates differential airway responses to acute and chronic antigen challenge. Repeated administration of dexamethasone and Ro 20–1724 with each OvA exposure attenuted all of the chronic inflammatory responses: early and late phase responses, hyperreactivity and eosinophilia. [ABSTRACT FROM AUTHOR]

Ten female patients with asthma-like symptoms but negative asthma tests (study group) were compared with 10 female asthmatics in an exercise test with and without pretreatment with β2-stimulants. The aim was to determine whether the asthma-like symptoms in the patients of the study group could be explained by bronchoconstriction, circulatory abnormalities, or physical unfitness when provoked physically, and whether the exercise test could be used to distinguish these patients from asthmatics. Without pretreatment, the asthma group reacted with bronchoconstriction, as indicated by postexercise systematic changes in PEFR, FEV1, FVC, and SaO2, which were not seen in the study group. The groups differed in the ratings of "difficulty in getting air", as only the asthma group had significantly lower ratings when pretreated. The study group's mean test performance was 94 W; the asthma group's was 106 W. The low performance was not explained by disturbances in heart rate, electrocardiogram, or blood pressure or physical unfitness. The exercise test was found to distinguish between the groups, especially for bronchoconstriction, oxygen saturation, and ratings of dyspnea. It could be used complementary to lung function tests to eliminate bronchoconstriction, circulatory abnormalities, and physical unfitness as a cause of the asthma-like symptoms. [ABSTRACT FROM AUTHOR]

A group of nine patients with respiratory symptoms after nonspecific irritating stimuli, but without any IgE-mediated allergy or demonstrable bronchial obstruction, were referred to the asthma/allergy outpatient department for evaluation of suspected asthma. In order to find a provocation model and objectively assess these patients' symptoms in controlled studies, provocation with perfume or placebo was performed. The same patients were also subjected to perfume provocation with or without a carbon filter mask to ascertain whether breathing through a filter with active carbon could prevent the symptoms. The patients breathed through the mouth during the provocations, as they used a nasal clamp to prevent any smell of perfume. We found that the patients' earlier symptoms could be verified by perfume provocation. Breathing through the carbon filter had no protective effect. The conclusion is that symptoms suggesting hyperreactivity of the respiratory tract and asthma can be provoked by perfume without the presence of bronchial obstruction, and that using a carbon filter mask has no preventive effect. The symptoms are not transmitted via the olfactory nerve, since the patients could not smell the perfume. but they may have been induced by a trigeminal reflex via the respiratory tract or by the eyes. [ABSTRACT FROM AUTHOR]

All eight production workers from a small trout-processing factory were studied because of respiratory or rhinitis symptoms when working next to the automatic gutting machine. Seven of the eight had positive histamine provocation tests. Four patients had elevated total IgE levels while one had a slightly elevated eosinophil count. All workers had either weakly or moderately positive RAST against contaminated water from the outlet drain of the gutting machine. This water contained 1 ng endotoxin/ml. We concluded that five of the workers had probably developed occupationally related asthma from inhalation of contaminated aerosol from the gutting machine. Inhalation of endotoxin from gram negative bacteria may be the cause of this disorder. An alternative explanation is a Type I allergy caused by fish or bacterial protein with or without a simultaneous effect of endotoxin. [ABSTRACT FROM AUTHOR]

The non-specific bronchial reactivity Following bronchial allergen challenge was studied in 40 patients with allergic bronchial asthma, particularly in subjects without definite late reactions 6 h after the provocations (reduction in peak expiratory flow or forced expiratory volume in 1 s of less than 15% of the control value at this time). Among a group of 21 patients submitted to bronchial provocation tests, 13 carried out maximal exercise tests 6 h and 1 week after the allergen challenge. In another group of 19 patients, the bronchial hyperreactivity to methacholine was assessed before and 6 h and 1 week after challenge. Two patients with a dual response (early + late) reacted with bronchial obstruction to the exercise. Exercise tests performed after I week did not provoke asthma in any patient. In the methacholine group a marked increase in responsiveness to methacholine 6 h alter the provocation was observed in those patients with a dual response who were tested and in those with equivocal late reactions and even in three patients with an isolated immediate reaction. The increased responsiveness was still present in many patients 1 week after challenge. The airway caliber did not influence the degree of responsiveness to methacholine. Nor did the degree of responsiveness have any influence on the patterns of reactions observed after allergen exposure. It was concluded that in some individuals exposure to the relevant allergen predisposes them to exercise-inducible bronchial obstruction. Further, it was confirmed that non- specific bronchial reactivity can be increased not only in patients with late responses - both definite and equivocal - but also in some patients with immediate reactions alone. It is suggested that only allergens provoking late reactions or an increase in the non-specific reactivity should be considered clinically relevant. [ABSTRACT FROM AUTHOR]

There is a lack of established criteria to identify asthma and bronchial hyperreactivity (BHR) in epidemiological studies, although both conditions appear to bear some relationship to atopy, at least in children. Recent studies indicate a low prevalence of atopy in former Socialist countries in Europe, yet the prevalence of BHR has been reported to be high. We have analysed the relationship between the outcome of various lung function tests, atopy and clinical symptoms of bronchial asthma in an epidemiological survey of Estonian 10-12 year old schoolchildren. Metacholine provocation test (four steps with the cumulative doses 100, 300, 700 and 1100μg), exercise challenge test and PEF-variability over two weeks were done in 806 children in Tallinn (coastal, industrialised city) and 774 children in Tartu (inland, university town). A positive response to the metacholine challenge test was recorded in 19% in Tallinn and in 32% in Tartu (p<0.001). A similar tendency was observed for a more than 15% decrease of FEV1 in the exercise challenge test, i.e. 6% in Tallinn and 18% in Tartu. There was only a weak relationship between BHR, as defined by either a positive metacholine challenge and/or exercise test, diagnosed asthma and reported wheezing. Thus, 47% of the wheezing children and 30% of the children with asthma had negative test results. Only 17% of the children with a positive metacholine challenge were atopic, as defined by at least one positive skin prick test. In conclusion, none of the methods employed to assess bronchial hyperresponsiveness were very useful for the identification of wheezing and asthmatic children in this epidemiological study. In contrast to the results of studies in Western Europe, most children with bronchial hyperreactivity in Estonia are not atopic. [ABSTRACT FROM AUTHOR]

Bronchial obstruction, its reversibility, airway hyperreactivity and inflammation are key variables of asthma. In clinical practice they can be assessed with repeated noninvasive lung function measurements (spirometry and mucociliary clearance). The asthmatic inflammation in contrast to chronic bronchitis is characterized by increased IgE and eosinophils depending on the disease state (seasonal, perennial, chronic symptomatic or asymptomatic asthma). Based on the above-mentioned clinically applicable measurements, a classification of asthma, chronic (obstructive) bronchitis, and emphysema is proposed because the three groups of diseases have different etiology and need different prophylactic and symptomatic treatment. [ABSTRACT FROM AUTHOR]