Nonspecific Bronchial Hyperresponsiveness Research Articles

Application of the New Asthma-Specific Job Exposure Matrix: A Study in Quebec Apprentice Cohort Exposed to Isocyanates

Background: Recently, the first asthma-specific Job Exposure Matrix (JEM) was updated to occupational asthma-specific JEM (OAsJEM). Our study aimed to evaluate the association between continued exposure to isocyanates and incident work-related chest symptoms in former car-painting apprentices and to compare the associations using the first and new OAsJEMs.Methods: We used data from an inception cohort of male car-painting apprentices. Post-apprenticeship exposure to isocyanate during follow-up was evaluated using the first asthma-specific JEM (“exposed”=1 or “not exposed”=0) and the new OAsJEM (high=2, medium=1, and none=0). Association between occupation exposure to isocyanate and incidence of work-related rhinoconjunctival and chest symptoms were evaluated through cox regression models, adjusted for age, smoking, wheezing, and non-specific bronchial hyperresponsiveness. Results: The agreement between the two JEMs (exposed vs non-exposed to isocyanate) was perfect (kappa coefficient=0.946, p<0.001). There were only five subjects who were classified as non-exposed based on the first JEM, but had a medium exposure to isocyanate based on the new OAsJEM. Exposure to isocyanate increased the risk of occupational chest symptoms in the high-exposure category (hazard ratio [HR] 2.7, 95% CI 1.1 – 6.6) and the medium category (HR 2.9, 95% CI 0.3 – 30.0) compared to the reference group based on the new OAsJEM, whereas an HR of 2.5 (95% CI 1.0-6.2) was observed from the first JEM. Both JEMs yielded an inconclusive association between exposure to isocyanates and the risk for work-related rhino-conjunctivitis. Conclusion: The asthma-specific JEM and OAsJEM consistently showed that isocyanate exposure increased the risk of incident work-related chest symptoms.

Irritant-Induced Asthma

Irritant-induced asthma (IIA) is a phenotype of asthma caused by the inhalation of irritant agents. Definite, probable, or possible IIA have been described, depending on the concentration of the inhaled irritants and the onset of respiratory symptoms respective to the time of exposure. Definite IIA represents approximately 4% to 14% of all cases of new-onset work-related asthma. Agents responsible for IIA can be encountered as fumes, gases, aerosols, or dusts. The most frequent are chlorine, nitrogen oxides, sulfur dioxide, ammonia, acetic acid, solvents, and cleaning materials. Although the diagnosis of definite IIA is based on a suggestive clinical history along with evidence of reversible airflow limitation and/or nonspecific bronchial hyperresponsiveness, possible IIA cannot be diagnosed with certainty because the relationship between exposure and the onset of symptoms is difficult to establish. This article reviews the epidemiology, pathophysiology, diagnostic approach, and management of IIA.

Assessment and outcomes of firefighter applicants with possible asthma.

Firefighter applicants (FFAs) with a history of asthma may be refused entry to the fire service because of potentially putting themselves and others at risk. We undertook a service evaluation to identify respiratory and employment outcomes of FFAs with a history of asthma who had undergone additional respiratory assessment at our specialist occupational lung disease clinic during 2005-19. We reviewed FFA medical records and categorized them as having either no current asthma or definite/probable asthma at the time of clinic assessment. 'No current asthma' was defined as negative non-specific bronchial hyper-responsiveness (BHR) to histamine/methacholine, and no symptoms or treatment within the 2 years before clinic. 'Definite/probable current asthma' was defined as either positive BHR, or negative BHR with symptoms and/or treatment within the previous 2 years. Around 1 year later, we contacted FFAs to enquire about their application outcome and current respiratory symptoms. Data were available on 116 applicants; of whom, 45% (n = 52) had definite/probable current asthma and were significantly more likely to be older, atopic to common aeroallergens, report atopic disease and have a lower forced expiratory volume in one second/forced vital capacity ratio compared with applicants with no current asthma. Only two individuals' applications were rejected due to asthma. At follow-up, just 2 (2%) of the 90 operational firefighters reported any recent trouble with asthma. A history of asthma alone is not sufficient to determine current asthma in FFAs. Even with a diagnosis of current asthma, FFAs are mostly successful in their application to join the fire service.

Macrolides versus placebo for chronic asthma.

Macrolides versus placebo for chronic asthma.

Asthma Phenotypes and Host Risk Factors Associated With Various Asthma-Related Outcomes in Health Workers.

Background: Work-related asthma phenotypes in health workers (HWs) exposed to cleaning agents have not been investigated extensively as other occupational exposures. This study aimed to describe asthma phenotypes and to identify important host risk factors associated with various asthma-related outcomes.Methods: A cross-sectional study of 699 HWs was conducted in two large tertiary hospitals. A total of 697 HWs completed questionnaire interviews. Sera collected from 682 HWs were analyzed for atopy (Phadiatop) and IgE to occupational allergens (NRL—Hev b5, Hev b6.02; chlorhexidine and ortho-phthalaldehyde—OPA). Methacholine (MCT), bronchodilator challenge (BDR) and fractional exhaled nitric oxide (FeNO) were performed. An asthma symptom score (ASS) used five asthma-related symptoms reported in the past 12 months. Current asthma was based on use of asthma medication or an asthma attack or being woken up by an attack of shortness of breath in the past 12 months. Nonspecific bronchial hyperresponsiveness (NSBH) was defined as having either a positive MCT or a significant bronchodilator response. Two continuous indices of NSBH [continuous index of responsiveness (CIR) and dose-response slope (DRS)] were calculated.Results: The prevalence of current asthma was 10%, atopic asthma (6%) and non-atopic asthma (4%). Overall, 2% of subjects had work-related asthma. There was a weak positive association between NSBH and FeNO [CIR: Beta coefficient (β) = 0.12; CI: 0.03–0.22 and DRS: β = 0.07; CI: 0.03–0.12]. Combining FeNO ≥ 50 ppb with a BDR [mean ratio (MR) = 5.89; CI: 1.02–34.14] or with NSBH (MR = 4.62; CI: 1.16–18.46) correlated better with ASS than FeNO alone (MR = 2.23; CI: 1.30–3.85). HWs with current asthma were twice as likely to be atopic. FeNO was positively associated with atopy (OR = 3.19; CI: 1.59–6.39) but negatively associated with smoking status (GMR = 0.76; CI: 0.62–0.94). Most HWs sensitized to occupational allergens were atopic.Conclusion: Atopic asthma was more prevalent than non-atopic asthma in HWs. Most asthma-related outcomes were positively associated with allergic predictors suggesting a dominant role for IgE mechanisms for work-related symptoms and asthma associated with sensitization to OPA or chlorhexidine.

Occupational Asthma Caused by Quaternary Ammonium Compounds: A Multicenter Cohort Study

Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n= 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. Most subjects with QAC-induced OA were working in the health care sector (n= 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P < .001). This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.

Inhalation Challenge Tests in Occupational Asthma: Why Are Multiple Tests Needed?

Occupational and environmental lung diseases are on the rise because of the widespread use of various toxic agents in industry. Asthma etiopathogenesis is unclear because of exposure to high and low molecular agents in workplaces. Approximately 15-25% of asthma in adults is reported to be related to occupational exposure. The prevalence of occupational asthma (OA) is predicted to be high. The difficulties in diagnosing OA results in inadequate treatment, permanent airway damage, and medicolegal and social problems. As with other occupational diseases, it is necessary to demonstrate a direct causal relationship between the suspected agent and OA. Spirometry, peak expiratory flow rate, and/or non-specific bronchial hyperresponsiveness are frequently used to show airway hyperresponsiveness at the workplace and away from work. However, there are some controversies about the specificity and sensitivity of these test methods. Furthermore, these tests do not identify the exposure agent, which could be the causative agent. Specific inhalation challenge (SIC) tests that demonstrate the direct causal relationship are currently the gold standard. However, their positive and negative predictive values have not yet been established; therefore, many low molecular weight agents could cause late or atypical reactions. Therefore, a negative SIC test cannot exclude the disease. This review describes the procedures for the SIC test and discusses the importance of using the combined test methods with the SIC test.

Pulmonary Function Testing in Work-Related Asthma: An Overview from Spirometry to Specific Inhalation Challenge.

Work-related asthma (WRA) is a very frequent condition in the occupational setting, and refers either to asthma induced (occupational asthma, OA) or worsened (work-exacerbated asthma, WEA) by exposure to allergens (or other sensitizing agents) or to irritant agents at work. Diagnosis of WRA is frequently missed and should take into account clinical features and objective evaluation of lung function. The aim of this overview on pulmonary function testing in the field of WRA is to summarize the different available tests that should be considered in order to accurately diagnose WRA. When WRA is suspected, initial assessment should be carried out with spirometry and bronchodilator responsiveness testing coupled with first-step bronchial provocation testing to assess non-specific bronchial hyper-responsiveness (NSBHR). Further investigations should then refer to specialists with specific functional respiratory tests aiming to consolidate WRA diagnosis and helping to differentiate OA from WEA. Serial peak expiratory flow (PEF) with calculation of the occupation asthma system (OASYS) score as well as serial NSBHR challenge during the working period compared to the off work period are highly informative in the management of WRA. Finally, specific inhalation challenge (SIC) is considered as the reference standard and represents the best way to confirm the specific cause of WRA. Overall, clinicians should be aware that all pulmonary function tests should be standardized in accordance with current guidelines.

Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms

Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negativeSIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma.

Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.

Bronchial Response to High and Low Molecular Weight Occupational Inhalant Allergens.

PurposeOccupational asthma may be induced by high- or low-molecular weight allergens (HMWA or LMWA, respectively). The study was conducted to compare the pattern of bronchial response in 200 HMWA-induced asthmatics (n = 130) and LMWA-induced asthmatics (n = 70).MethodsThe study participants underwent a single-blind, placebo-controlled specific inhalation challenge (SIC) with workplace allergens, accompanied by evaluation of non-specific bronchial hyperresponsiveness (NSBHR) with methacholine before and after the SIC.ResultsA single early bronchial response more frequently occurred in HMWA-induced asthmatics than in LMWA-induced asthmatics (86.2% vs. 20%). An isolated late bronchial response or atypical patterns were more frequently observed in LMWA-induced asthmatics than in LMWA-induced asthmatics (45.7% vs. 3.8% or 34.3% vs. 10%, respectively). Baseline NSBHR before SIC was more often detected in LMWA-induced asthmatics than in HMWA-induced asthmatics (81.4% vs. 54.6%), and the median value of the provocation concentration of methacholine was relevantly lower in these patients before and after SIC. A significant 3-fold increase in NSBHR after SIC was observed more often in LMWA-induced asthmatics than in HMWA-induced asthmatics (82.8% vs. 66.1%). In addition, compared to LMWA-induced asthmatics, HMWA-induced asthmatics were older, were more frequently active smokers, showed lower level of NSBHR, and more frequently continued their work in harmful occupational exposure.ConclusionsThe results of this study suggest that HMWA-induced asthmatics may have milder clinical courses and that there is a possibility of job continuation despite asthma exacerbation requiring medical surveillance.

Novel clinical scores for occupational asthma due to exposure to high-molecular-weight agents

ObjectiveSpecific inhalation challenge (SIC) as the reference diagnostic test for occupational asthma (OA) is not widely available worldwide. We aimed to develop non-SIC-based models for OA.MethodsOf 427 workers who were...

Physiotherapy improves symptoms of exercise-induced laryngeal obstruction in young elite athletes: a case series

ObjectiveA constricted, upper chest breathing pattern and postural dealignments habitually accompany exercise-induced laryngeal obstruction (EILO), but there are few effective treatments for athletes presenting with EILO. This case series was...

Relationship between Serum Omega-3 Fatty Acid and Asthma Endpoints.

Recent studies have highlighted the potential protective role of omega-3 polyunsaturated fatty acids (n-3 PUFA) in asthma. This study aimed at determining the association between seafood intake, serum PUFA composition and clinical endpoints of asthma in adults. A cross-sectional study of 642 subjects used the European Committee Respiratory Health Survey (ECRHS) questionnaire, skin prick tests, spirometry and methacholine challenge tests following ATS guidelines. Sera was analysed for n-3 and n-6 PUFA composition. Subjects had a mean age of 34 years, were largely female (65%) and 51% were current smokers. While 99% reported fish consumption, rock lobster, mussels, squid and abalone were also consumed less frequently. The prevalence of asthma symptoms was 11%, current asthma (ECRHS definition) was 8% and non-specific bronchial hyperresponsiveness (NSBH) was much higher (26%) In adjusted models the n-3 PUFAs 20:5 (EPA) and 22:5 (DPA) were significantly associated with a decreased risk of having NSBH. Total n-3 PUFA composition was associated with decreased NSBH risk (OR = 0.92), while high n-6 PUFA composition was associated with an increased risk (OR = 1.14).

The MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up

The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease.The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease.Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.

Estudio de los mecanismos implicados en la génesis y evolución del asma (proyecto MEGA): creación y seguimiento a largo plazo de una cohorte de pacientes asmáticos

The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease.The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease.Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.

Longitudinal observation of non-specific bronchial hyperresponsiveness in school children: The role of the Atopy

Longitudinal observation of non-specific bronchial hyperresponsiveness in school children: The role of the Atopy

Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma.

Ascertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC). The study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined. A concentration of histamine inducing a 20% decline in FEV1 (PC20 ) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb, or both outcomes. Combining either a PC20 value ≤16 mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC20 ≤16 mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%. Adding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.

Occupational allergy to food-derived allergens

Although most cases of food allergy are related to food ingestion, occupational exposure to foods by contact or inhalation may also lead to adverse reactions, inducing contact urticaria or dermatitis, asthma, rhinitis, hypersensitivity pneumonitis, and anaphylaxis. Almost 10–25% of cases of allergic occupational asthma and rhinitis are due to food products. Animal and vegetal high-molecular weight proteins derived from aerosolized foods during food processing or handling at the workplace, as well as additives used as preservatives and antioxidants, and food contaminants, are the main causal agents. Farmers who grow and harvest crops and workers employed in food processing, storage and packing, and those involved in food preparation and transport are considered at increased risk for developing food-induced occupational asthma and rhinitis. Bakers’ asthma is the most frequent type of occupational asthma all around the world. Seafood processing industry is also at higher risk for asthma and rhinitis. A proportion of cases of asthma and rhinitis in food industry is also related to latex gloves used during food processing. The diagnosis of food-related occupational asthma and rhinitis includes a careful clinical and occupational history, respiratory functional assessment and measurement of non-specific bronchial hyperresponsiveness, immunologic assessment and specific inhalation challenge. The management includes environmental interventions aimed to avoid or reduce exposure to the offending agent, pharmacologic therapy, and allergen immunotherapy when available. Only few cases of food-induced occupational anaphylaxis have been described. The management of these emergencies should follow the current guidelines on anaphylaxis. The worker should be educated in managing future possible episodes that may also occur out of the workplace, by instance after accidental ingestion of the culprit allergen, and to carry 2 pre-loaded adrenaline delivery systems and a MedicAlert bracelet.

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.