Nonspecific Bronchial Hyperreactivity Research Articles

Asthma: New Integrative Treatment Strategies for the Next Decades.

Asthma is a chronic disease whose main anatomical–functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

Spécificités de l’asthme professionnel chez les femmes et son interaction avec le statut hormonal

Occupational asthma (OA) is described as the most common respiratory disease in industrialized countries. A female predominance characterizes many populations of asthmatic workers. Differences in occupational exposures by gender as well as hormonal variations could affect OA in women. To identify the socio-occupational and medical characteristics of OA in women compared to men and to investigate a possible hormonal influence on OA in women. This is a retrospective study, based on medical records of out patients of the Department of Occupational Medicine during the period between 1st January 2009 and 30 June 2016 for OA completed by a phone call to collect missing data. Over 222 cases of OA, a female predominance was noted (60.81%), which was predominantly in the textile sector (61.5%). Clinically, men had more exercise dyspnea and wheezing, whereas the association with rhinitis was significantly greater in women. The majority of women with asthma had irregular menstrual cycles (46.2%), they were multiparous in 54%, menopaused in 13% of cases with a mean age of menarche of 12±1.65 years. A worsening of OA was noted in 58% of women during their perimenstrual period, 75% during pregnancy and 14% of women when taking hormonal contraceptives. In asthmatic women, only the presence of non-specific bronchial hyperreactivity was significantly associated with menarche age (P=0.007). Differences between men and women in OA with variability of symptoms during female genital life have been identified. Further studies to personalized care strategies for women need to be undertaken.

Survenue de symptômes tardifs après un test de provocation par la méthacholine

There are few prospective studies available on the development of delayed symptoms following challenge tests with methacholine (MCT) at the currently recommended doses. The objective of this study was to describe the nature and frequency of respiratory symptoms suggestive of bronchospasm developing within 24hours after a MCT. The study was offered to adult patients who underwent MCT seen consecutively between June and October 2015. Following the test, a questionnaire adapted from the GINA asthma control questionnaire bearing on diurnal and nocturnal symptoms (cough, dyspnoea, wheeze and tightness), was delivered to the patient and the replies collected by telephone 24hours later. Of the 101patients included (initial FEV1 2.82±0.79L), 46 (46%) were MCT+ and 55 (54%) MCT-. Among the MCT-, 4 (7%) presented with immediate symptoms (S+) and 4 (7%) with delayed symptoms. Among the MCT+ patients, 36 (78%) presented with immediate symptoms (P<0.001compared with the MCT- patients), and 39 (85%) with delayed symptoms (P<0.001compared with the MCT- patients). Delayed symptoms developed with a mean of 5h30after the provocation test. Immediate and delayed symptoms were more frequent in subjects having significant non-specific bronchial hyper-reactivity. Informing patients of the risk of developing delayed symptoms seems useful and allows optimization of their management after a MCT.

Non-Specific Bronchial Hyperreactivity measured by Methacholine in the Diagnosis of Asthma in Children

Non-Specific Bronchial Hyperreactivity measured by Methacholine in the Diagnosis of Asthma in Children

Does the medical diagnosis of occupational asthma coincide with the legal diagnosis?

ABSTRACTObjective: The incidence of occupational asthma (OA) is increasing worldwide. In this study, we first aimed to document the rate of diagnosis of OA among patients who were referred to our clinic from the Social Security Institution and the factors that affected diagnosis; secondly, we aimed to assess the consistency of the medical and legal diagnoses. Methods: The study involved 132 consecutive patients who were referred to our clinic for the evaluation of OA between 2010 and 2015. Detailed workplace history, the tools used in the diagnosis such as peak expiratory flow (PEF) monitoring and bronchial provocation tests, and the final medical diagnosis were recorded from case files. Results: Asthma was diagnosed in 75% (n = 99) of the patients. Among them, 22.2% were diagnosed as having OA. The diagnosis was confirmed by serial PEF measurements, non-specific bronchial hyperreactivity assessment or both of the tests both at work and off-work periods. OA diagnosis was mostly established in active workers (72.7%). The legal diagnosis period was completed in 54.5% of these 22 patients, and 50% (n = 11) were officially diagnosed as having OA with a 91.6% concordance with medical diagnosis. Conclusion: This study verifies the importance of diagnosing asthma correctly as a first step in the evaluation of OA. Diagnostic tests other than specific provocation tests could be preferential in patients who still work in the same field. We believe that cooperation with the patient's occupational physician and adequate recognition of the work environment will improve the consistency of legal and medical diagnoses.

Specific bronchial hyperreactivity and hypersensitivity in patients with allergic asthma

Background/Aim. Bronchial asthma is a disease that is characterized by the variability of the clinical picture, physical and functional status and the existence of bronchial hypersensitivity and hyperreactivity with varying degrees. Bronchial responsiveness and sensitivity are tested in patients with clinically suspected existence of asthma and normal spirometry test. The aim of the study was to analyze the patients with atopic asthma and study test results of skin sensitization to inhaled allergens, nonspecific bronchial hyperreactivity and specific hyperreactivity estimated by bronchial provocation tests with inhalant allergens. Methods. The prospective study at the Pulmonology Clinic of the Military Medical Academy in Belgrade Serbia, during 2014, included 70 male subjects aged 18?30 years, who had perennial asthma symptoms. All subjects were nonsmokers, with normal spirometry findings, with normal radiological chest findings and with no symptoms of respiratory infection over the past two months. All respondents were tested with skin prick tests with inhalant allergens and nonspecific bronchial provocation test with histamine. On the basis of histamine test, subjects were divided into two groups: the group I, in which there was a slight degree of hypersensitivity [provocation concentration of histamine causing a 20% fall in forced expiratory volume ? PC20 = 6.09 ? 1.1 mg/mL], and the group II with negative histamine test (PC20 = 14.58 ? 6.34 mg/mL). Specific bronchial provocation test was performed in all patients, and the selection of the allergens was carried out based on the results of testing of skin hypersensitivity. Results. Results of skin sensitization show the highest incidence of mites Dermatophagoides pterronissinus (83.3% group I and 85.0% group II) followed by grass pollen (53.3% group I and 52.0% group II), and house dust (33.3% group I and 50.0% group II). There were no statistically significant differences in allergens between groups (p &gt; 0.05). In both groups, spirometry findings were within normal values [forced vital capacity ? FVC and forced expiratory volume 1 ? FEV1 &gt; 80% predictive value], but statistically significant difference was found in FEV1 between groups (p &lt; 0.05). Specific bronchial provocation tests with solutions of inhaled allergens in both groups caused a significant decline in FEV1 (? 20%) in all patients individually. No statistically significant differences were found neither between groups, nor between individual allergens (average decline in FEV1: Group I 32.9 ? 2.4% and group II 31.5 ? 2.2%). Conclusion. There is no relationship between the degree of specific and non-specific bronchial hyperreactivity in patients with allergic asthma.

Occupational asthma compensation in the Tunisian Center: cross-sectional study over a period of eight years

IntroductionLes objectifs étaient de dresser le profil épidémiologique des patients indemnisés pour asthme professionnel dans le centre tunisien, identifier leurs caractéristiques professionnelles et évaluer les pratiques d’indemnisation de cette maladie professionnelle.MéthodesÉtude exhaustive rétrospective, menée sur une période de huit ans, à propos des cas d'asthme professionnel reconnus et indemnisés au centre tunisien par les deux seules commissions médicales habilitées à fixer le taux d’incapacité partielle permanente aux victimes des accidents de travail et des maladies professionnelles dans les sept gouvernorats du centre.RésultatsAu total, 129 travailleurs, d’âge moyen égal à 40,6 ± 7,75 ans étaient indemnisés pour asthme professionnel durant la période d’étude. Le sexe ratio était de 0,66. Les agents étiologiques les plus incriminés ont été les poussières végétales textiles (75,2%), les poussières de bois, la farine et les isocyanates. Une hyperréactivité bronchique non spécifique a été retrouvée dans 38%, un taux élevé d’IgE dans 14% et des prick tests positifs dans 10,9% des cas. Le taux moyen d’incapacité partielle permanente était de 25,6±14,2%. Ce taux était corrélé, selon l’analyse analytique, à l’âge du patient et à la commission médicale ayant fixé ce taux.ConclusionL’étude des cas d’asthme professionnels indemnisés, apportent des données pertinentes à propos des caractéristiques épidémiologiques et cliniques des patients atteints et des pratiques des comités notamment, en terme d’application du barème indicatif, mais ne permet pas l'appréciation de la prévalence, souvent sous-estimée de cette pathologie.

Weather conditions and climate change have an effect on allergies

Climate change particularly affects the health of vulnerable groups, such as children, the elderly, and socially disadvantaged individuals. Asthmatics are also at greater risk from the results of climate change due to their non-specific and allergen-specific bronchial hyperreactivity. Climate change affects the production, release, and number of allergenic pollens throughout Europe. Tree pollen in particular is being seen earlier and in greater numbers, while little effect is seen on grass pollens, and mugwort pollen is showing a downward trend. The ragweed that is spreading throughout Europe is still only of regional relevance in Germany. Thunderstorm periods represent a risk for pollen asthmatics. Although little is known about changes in molds, an increase in mycelium growth and spore formation is anticipated. Warmer winters may result in changes to mite populations.

Clinical efficiency of midget doses of the affine cleared antibodies to S-100 protein at the children with dysfunction of autonomic nervous system and acute obstructive bronchitis in anamnesis

The importance in a pathogenesis of the wheezing and a development of a nonspecific bronchial hyperreactivity belongs to neurogenic mechanisms. It is known that perinatal damage of the central nervous system are an adverse background for a forwardness of acute wheezing and bronchial asthma at children. The available data on a role of a functional condition of autonomic nervous system at the wheezing aren't numerous and rather contradictory that demands further researches, including in respect of a choice of methods of the rehabilitation. The aim of our study was to determine of the clinical and functional efficiency of including of midget doses of the affine cleared antibodies to S-100 protein in complex rehabilitation of the children of early age with wheezing, depending on the presence of mild severity of perinatal damage to the CNS hypoxic genesis. Our data showed that additional including of midget doses of the affine cleared antibodies to S-100 protein in a complex of rehabilitation of these patients a positive effect on the autonomic imbalance, vegetative component of the wheezing. At the same time, prescription by a short course (less 5 weeks) of midget doses of the affine cleared antibodies to S-100 protein didn't prevent emergence of episodes of the wheezing. Perhaps, patients with recurrent wheezing with the expressed functional disturbances of the autonomic nervous system, need longer courses of the this medicine that can be useful in a complex of rehabilitation.

Diagnostic value of the indices of nonspecific bronchial hyperresponsiveness for verification of bronchial asthma remission in teenagers

The results of an analysis of indices of nonspecific bronchial hyperreactivity in 63 adolescents with asthma in remission are presented in the article. It is established that the absence of bronchial hypersensitivity to inhalation of histamine at a concentration of less than 2,0 mg / ml, with high specificity (89,7 %) and post-test probability (29,8 %) indicates the presence of teenagers complete clinical-instrumental remission with probable ratio chance of this event, equal to 6,0.

Nonspecific bronchial hyperreactivity after exposure to Western Red Cedar.

A 55-year-old nonatopic man presented with a 2-year history of progressively severe conjunctivitis, rhinitis, and asthma related to exposure to freshly cut red cedar. Chest roentgenogram, lung volumes, diffusing capacity for carbon monoxide, and expiratory flow rates were normal. A histamine inhalation test demonstrated mild, nonspecific bronchial hyperreactivity. After a 35-min cumulative exposure to Western Red Cedar sawdust in the laboratory, the patient developed a late asthmatic response. Bronchial reactivity to inhaled histamine increased significantly after exposure to red cedar in the laboraotry and again after natural exposure to red cedar at work. However, on both occasions forced expiraotry volume in one sec was decreased when compared to control values. Exposure to red cedar sawdust for 15 min was repeated in the laboratory, and histamine inhalation tests were performed the day before, for 4 consecutive days after, and 11 days after exposure. Before each test, one-sec forced expiratory volume, lung volumes, specific conductance, maximal expiratory flow rates at 25 and 50 per cent of vital capacity, closing capacity, and the slope of phase III from the single-breath O2 test were measured. Six hours after exposure to cedar, all measurements documented significant airway obstruction that persisted until the second day. Bronchial responsiveness to inhaled histamine also increased on the first 2 days after exposure to cedar, but this increase persisted on the third and fourth day when all other pulmonary function tests had returned to control values. Eleven days later, the bronchial hyperreactivity to inhaled histamine had also returned to control values. In a sensitized subject, exposure to Western Red Cedar induced a transient increase in nonspecific bronchial reactivity that was present in the absence of airflow obstruction. Factors other than decreased airway caliber are probably important in this phenomenon.

Sublingual immunotherapy in children with allergic rhinoconjunctivitis mono-sensitized to house-dust-mites: A double-blind-placebo-controlled randomised trial

Although sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficient treatment in children with seasonal allergic rhinitis (AR), there is little evidence on the efficacy of SLIT with house-dust-mite (HDM) extract in children with isolated perennial AR. We sought to assess the clinical efficacy and safety of HDM-SLIT in children with isolated allergic rhinitis-conjunctivitis mono-sensitized to HDM without asthma symptoms. Twenty-two children (aged 5-10 years) with perennial AR and conjunctivitis symptoms mono-sensitized to Dermatophagoides pteronyssinus and Dermatophagoides farinae were enrolled. During a 2 months run-in period, symptom and medication scores, lung functions, bronchial hyperreactivity, nasal provocation and skin prick tests were evaluated. Subjects were randomized to active or placebo using a double-blind method. A total of eighteen subjects were randomised to receive either active SLIT or placebo for 12 months. Daily symptom and medication scores, baseline lung functions, bronchial hyperreactivity, nasal provocation and skin prick tests were recorded and re-evaluated at the end of treatment. After one year of treatment, no significant differences were detected in the between groups and within group comparisons based on total rhinitis symptom/medication scores (p > 0.05). Skin reactivity to Dermatophagoides pteronyssinus was significantly reduced in HDM-SLIT compared to placebo group (p = 0.018). A significant reduction in nasal sensitivity was observed in SLIT group after one year treatment when compared to baseline (p = 0.04). Total conjunctivitis symptoms were reduced significantly in both active and lacebo group at the end of treatment compared to baseline. The proportion of patients with non-specific bronchial hyperreactivity increased to almost 3-fold in placebo group compared to baseline. HDM-SLIT was not superior to placebo in reducing isolated rhinoconjunctivitis symptoms within 12 months of treatment. However, HDM-SLIT has a modulating effect on allergen-specific nasal and skin reactivity in isolated perennial AR children. The trial was registered at Anzctr.org.au number, ACTRN12613000315718.

Occupational Asthma in Female Factory Worker Resulting from Exposure to Savinase in Dishwashing Tablets—A Case Study

Savinase is one of the endopeptidases widely used in washing detergents. Its ability to cause respiratory allergy has been known. Up to now, most cases of occupational asthma (OA) to savinase have been described among workers involved in the manufacture of laundry detergents. We present a case study of 51-year-old female worker of a dishwashing tablets factory, who had been packaging ready-made tablets into foil wrappers for 4 years and developed respiratory symptoms, such as cough, dyspnoea and wheezing. A number of clinical procedures were performed, including the clinical examination, routine laboratory tests, evaluation of total and allergen-specific serum IgE (asIgE) to enzymes, skin prick tests for common allergens, rest spirometry, inhalation methacholine challenge test and a single-blind, placebo-controlled specific inhalation challenge test (SICT) with dishwashing tablets. Clinical findings and results of routine laboratory tests were within normal limits. Baseline nonspecific bronchial hyperreactivity was revealed. In patient's serum blood we found significantly elevated asIgE to savinase. Decline of FEV1 and PEF in late phase of asthmatic reaction was observed during the specific challenge test. The patient reported chest tightness between 5-12 hours after exposure to dishwashing tablet ingredients. Cytological assessment of an induced sputum revealed increase in the percentage of eosinophils 24 hours after specific challenge in comparison to values noted before the SICT. Positive clinical response to the challenge confirmed in objective method tests validated the diagnosis of OA.

Asthme professionnel aux produits de pyrolyse des matières plastiques dans une entreprise de fabrication de masques de protection respiratoire. À propos de deux cas

The process of making masks for adsorbing gases and vapors acids uses many materials including polyolefins (polyethylene/polypropylene) but also activated carbon. Thus during the process of making these masks, these polyolefins, which are thermoplastic resins produced from ethylene (polyethylene) or propylene (polypropylene) are subjected to high temperatures (>300°C), will depolymerize and emit vapors containing particularly aldehydes including formaldehyde, which are both irritating and respiratory sensitizers. ObjectivesTo study the environmental determinants of two cases of asthma occurred during labor in the manufacturing industry of respiratory protection masks. Materials and methodAnamnestic, functional, allergy and environmental study of two cases of asthma occurred in a manufacturing respiratory protection masks against acid gases and organic vapors having accessed the service of occupational medicine and occupational diseases at Rabta Hospital between 2007 and 2009. ResultsThis is a series of two women with a mean age of 39.5years, an average tenure in the company of 20years and an average tenure in the mask making of 5years with confirmed atopy and who consulted for asthma symptoms appeared a few months after the establishment of the factory masks. Exploring functional objectified reversible obstructive syndrome in the first case and a positive test of nonspecific bronchial hyperreactivity in the second case. The study post revealed that the material of masks was composed especially of polyolefins and activated charcoal generating a noticeable release of vapors in thermoforming station masks at a temperature of 384°C. In view of these environmental data, the diagnosis of occupational asthma has been made in the two cases. Because this process of thermoforming at 384°C allows the release of pyrolysis products of plastics and therefore several irritating and allergenic substances including formaldehyde essentially, we withhold the latter presumptively as the causative agent for the two cases of asthma. This asthma is aggravated by activated charcoal dust known for its irritant high power and may explain the reported generalized pruritus. ConclusionsThe risks associated with emissions from thermal degradation of polyolefins justify clinical monitoring very useful in many cases. In undertaking our study, preventive measures were recommended including better hygiene and improved local exhaust ventilation to the thermoforming station masks.

Workplace interventions for treatment of occupational asthma

The impact of workplace interventions on the outcome of occupational asthma is not well-understood. To evaluate the effectiveness of workplace interventions on the outcome of occupational asthma. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; NIOSHTIC-2; CISDOC and HSELINE up to February 2011. Randomised controlled trials, controlled before and after studies and interrupted time series of workplace interventions for occupational asthma. Two authors independently assessed study eligibility and trial quality, and extracted data. We included 21 controlled before and after studies with 1447 participants that reported on 29 comparisons.In 15 studies, removal from exposure was compared with continued exposure. Removal increased the likelihood of reporting absence of symptoms (risk ratio (RR) 21.42, 95% confidence interval (CI) 7.20 to 63.77), improved forced expiratory volume (FEV1 %) (mean difference (MD) 5.52 percentage points, 95% CI 2.99 to 8.06) and decreased non-specific bronchial hyper-reactivity (standardised mean difference (SMD) 0.67, 95% CI 0.13 to 1.21).In six studies, reduction of exposure was compared with continued exposure. Reduction increased the likelihood of reporting absence of symptoms (RR 5.35, 95% CI 1.40 to 20.48) but did not affect FEV1 % (MD 1.18 percentage points, 95% CI -2.96 to 5.32).In eight studies, removal from exposure was compared with reduction of exposure. Removal increased the likelihood of reporting absence of symptoms (RR 39.16, 95% CI 7.21 to 212.83) but did not affect FEV1 % (MD 1.16 percentage points, 95% CI -7.51 to 9.84).Two studies reported that the risk of unemployment after removal from exposure was increased compared with reduction of exposure (RR 14.3, 95% CI 2.06 to 99.16). Three studies reported loss of income of about 25% after removal from exposure.Overall the quality of the evidence was very low. There is very low-quality evidence that removal from exposure improves asthma symptoms and lung function compared with continued exposure.Reducing exposure also improves symptoms, but seems not as effective as complete removal.However, removal from exposure is associated with an increased risk of unemployment, whereas reduction of exposure is not. The clinical benefit of removal from exposure or exposure reduction should be balanced against the increased risk of unemployment. We need better studies to identify which interventions intended to reduce exposure give most benefit.

Diagnosing of bakers' respiratory allergy: Is specific inhalation challenge test essential?

The diagnosis of occupational asthma (OA) and/or rhinitis needs to be confirmed by means of objective methods, because it is followed by important social and financial consequences. The aim of the study was to evaluate sensitivity and specificity of diagnostic methods as skin-prick tests (SPTs) to occupational allergens, evaluation of allergen-specific serum IgE, and nonspecific bronchial hyperreactivity with reference to a specific inhalation challenge test in diagnosing bakers' respiratory allergy due to wheat flour. The study group included 358 bakers suspected of having OA due to wheat flour. They underwent physical examination, SPTs to common and occupational allergens, allergen-specific IgE determination, spirometry, nonspecific bronchial challenge, and specific inhalation test. The sensitivity of SPTs to occupational allergens in recognition of baker's rhinitis was low (47.9%) unlike the estimation of allergen-specific IgE (76.4%), with relatively high specificity (77.4 and 68.3%, respectively). Bronchial hyperreactivity (PC(20) < 8 mg/mL) was the most sensitive method, whereas high degree of bronchial hyperreactivity (PC(20) < 1 mg/m(3)) alone or bronchial hyperreactivity (PC(20) < 8 mg/m(3)) combined with the skin reactivity to wheat flour was the most specific method of recognizing OA. Neither SPTs to occupational allergens nor evaluation of serum allergen-specific IgE alone or combined with nonspecific bronchial hyperreactivity are characterized by sufficient diagnostic accuracy to replace the specific inhalation challenge test. For the establishment of a definite diagnosis of baker's asthma, specific challenge testing with occupational allergens should be performed.

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.

P7 Occupational eosinophilic constrictive bronchiolitis with asthma in a foam cutter caused by Soya bean products

Introduction and backgroundSoya bean dust is a recognised cause of asthma. More recently Soya bean has bean used in the manufacture of foam. The main market for this ‘environmentally friendly...

Serum immunoglobulin levels as a predictive factor for a better outcome of non-atopic childhood asthma

Childhood asthma is a heterogeneous condition with different phenotypes. Hereby, we aimed to study impact of serum immunoglobulin levels on clinical phenotypes and outcome of asthma. Seventy-eight children (M: 26, F: 52) aged less than 10 yrs (mean = 8.56 ± 3.23 yrs) and diagnosed as mild-moderate persistent asthma, followed up for at least 1 yr were included into the study. Asthmatic children were divided into two groups based on serum immunoglobulin levels at admission and were evaluated with respect to demographic data, allergic sensitization, symptom scores, medication usage, pulmonary functions, and non-specific bronchial hyper-reactivity. The age at onset of symptoms (40.88 ± 32.02 vs. 23.04 ± 26.97 months) was significantly younger in children with hypogammaglobulinemia (n = 28) compared to normogammaglobulinemia group (n = 50) (p = 0.016). Mean follow-up duration was 3.8 ± 2.1 yrs. Atopic sensitization rate was higher in those with normal immunoglobulin levels (81.2% vs. 17.9%), (p < 0.0001). Normal serum immunoglobulin levels were associated with atopic asthma (OR, 4.5; 95% confidence interval (CI): 2.0-10.1). For the prediction of atopic asthma, having normal immunoglobulin levels yielded predictive values of: sensitivity = 88.6%, specificity = 71.8%, positive predictive value = 81.1%, negative predictive value = 82.1%. Furthermore, percentages of atopic dermatitis and allergic conjunctivitis, elevated serum total IgE levels, eosinophilia, and bronchial hyper-reactivity were more common in normogammaglobulinemia with asthma group (p = 0.040, p = 0.003, p = 0.024, p = 0.030, p = 0.040, respectively). Although marked reductions in asthma scores and inhaled corticosteroid usage were observed in both groups over time, the rate of decline was significantly higher and earlier in hypogammaglobulinemia group (p = 0.0001, p = 0.004, respectively). In conclusion, asthmatic children with hypogammaglobulinemia presented at an earlier age, with lower rates of atopy, and earlier clinical improvement accompanied with earlier discontinuation of inhaled corticosteroids than children with normal immunoglobulin levels. Our data demonstrated that in children currently named as early-onset non-atopic asthma, hypogammaglobulinemia might be accompanying, providing evidence for a different phenotype of childhood asthma.

Inflammation and functional outcome in diisocyanate‐induced asthma after cessation of exposure

The clinical outcome of diisocyanate-induced asthma has been found to be poor despite cessation of exposure. Our aim was to study the outcome of diisocyanate-induced asthma after initiation of inhaled steroid treatment at a mean period of 7 months (range 2-60 months) after cessation of exposure by following up lung function and bronchial inflammation. Bronchoscopy was performed on 17 patients 2 days after a positive inhalation challenge test, after which budesonide 1600 mug a day was started. Bronchoscopy, spirometry, and histamine challenge tests were repeated at 6 months and on average 3 years. The results were also compared with those obtained from 15 healthy control subjects. Nonspecific bronchial hyperreactivity diminished significantly (P = 0.006); however, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) values decreased, with a median yearly reduction of FEV1 of 79 ml. The count of mast cells in bronchial mucosa decreased (P = 0.012) and that of macrophages increased (P = 0.001). Interleukin-4 level in mucosa was during the first year significantly higher than in controls but its level decreased in the follow-up. Interleukin-6, interleukin-15, and tumour necrosis factor alpha messenger-RNA levels were significantly higher in hyperreactive patients than in nonhyperreactive patients at the end of the follow-up. Our results indicate that inflammation may persist in diisocyanate-induced asthma despite inhaled steroid medication. However, TH2-type inflammation diminished. Persistent nonspecific bronchial hyperreactivity was associated with proinflammatory acting cytokines produced mainly by macrophages. Considering the poor prognosis of the disease the findings could be utilized to develop the follow-up and treatment of diisocyanate-induced asthma.