Bronchial Challenge Research Articles

The Efficacy of the Dyson Air Purifier in Improving Asthma Control: Protocol for a Single-Center, Investigator-Led, Randomized, Double-Blind, Placebo-Controlled Trial.

BackgroundIndoor air quality has been shown to influence asthma control and outcomes. Air purifiers and high-efficiency particulate air filtration devices can improve indoor air quality by reducing the indoor levels of air pollution and allergens. However, the influence of this improved indoor air quality on asthma control remains unclear; hence, randomized controlled trials are needed to further elucidate this phenomenon.ObjectiveThis study aims to investigate the effect of reducing the levels of allergens and pollutants in the bedroom and living room through the use of Dyson air purifiers (Dyson Pure Cool) on asthma control.MethodsThis is an 18-month long, investigator-led, randomized, double-blinded, placebo-controlled, single-center trial. Subjects will be randomized in a 1:1 ratio to active or placebo Dyson filters. The primary outcome is the change in the scores of Asthma Control Questionnaire 6 and Asthma-specific Quality of Life Questionnaire from baseline. Secondary outcomes include changes in lung function (forced expiratory volume in one second, forced expiratory volume in one second/forced vital capacity ratio, and midexpiratory flows), peak expiratory flow measurements, airway hyperresponsiveness (assessed by methacholine bronchial challenge), fractional exhaled nitric oxide, and indoor air pollutant levels. The sample size will be 50 subjects, and all subjects will have a confirmed diagnosis of mild persistent to moderate persistent asthma along with an Asthma Control Questionnaire 6 score of >1.5.ResultsThis study was approved by the West Midlands Research Ethics Committee (18/WM/0277). The study results will be published in peer-reviewed scientific journals; presented at relevant scientific conferences; and shared in plain English with participants in our newsletters, in our clinics, and via the David Hide Asthma and Allergy Research Centre website. Our trial began in September 2019 and is expected to end in August 2021.ConclusionsThis is a double-blinded, placebo-controlled, randomized, investigator-led study to investigate the efficacy of a novel air purifier in improving asthma control in adults. The trial period of 18 months will facilitate the collection of robust data and will therefore generate clear signals. However, this extended trial duration may lead to patient withdrawal. Furthermore, this trial is conducted at a single center and in a location with a homogenous cohort of people, which may affect translatability. Nonetheless, it is hoped that the findings of this trial may help further inform clinicians regarding the utility of this novel device as an adjunct in asthma care.Trial RegistrationClinicalTrials.gov NCT04729530; https://clinicaltrials.gov/ct2/show/NCT04729530International Registered Report Identifier (IRRID)DERR1-10.2196/28624

Diagnosing Asthma with and without Aerosol-Generating Procedures

Asthma diagnostic guidelines require procedures with aerosol-generating potential (aerosol-generating procedures [AGPs]) to guide decision making. Restricted access to AGPs poses significant challenges in primary care and resource-poor countries, further amplified during the coronavirus disease 2019 pandemic. To establish an approach to asthma diagnosis that does not require AGPs. Symptomatic yet untreated (beyond as-required bronchodilator use) adults with clinician-suspected asthma and maximum 10 pack year smoking history were recruited. Clinical history, physical examination, spirometry with bronchodilator reversibility, home peak flow monitoring, and bronchial challenges were performed, and fractional exhaled nitric oxide and serum eosinophils measured. Tests were then repeated following treatment with inhaled corticosteroids before an asthma diagnosis was confirmed or refuted by an expert panel. A total of 65 adults (mean age, 34.8 ± 12.2 years) were recruited. Five were excluded as "unclassifiable," because of borderline results or missing data. Of the remainder, 36 were diagnosed with asthma and 24 were not. Using data from non-AGPs only (wheeze on auscultation and blood eosinophilia) and home peak flow variability, a "rule-in" diagnostic model provided comparable discriminative ability to the application of established guidelines. Clinical suspicion of asthma together with at least 1 positive non-AGP test result provided a sensitivity of 55%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 60%. Application of this model reduced the need for spirometry-based tests by one-third. The proposed diagnostic algorithm may be clinically useful in "ruling-in" asthma in adults when access to AGPs is limited. This algorithm is not suitable for those with low clinical probability, with a significant smoking history, or where alternative diagnoses are more likely. This pragmatic approach to asthma diagnosis merits prospective validation.

Local Respiratory Allergy: From Rhinitis Phenotype to Disease Spectrum.

Local respiratory allergy (LRA) is defined by the negativity of atopy tests, a clinical history suggestive of airway allergy and a positive response to the nasal and/or bronchial allergen challenge. The clinical spectrum of LRA is comprised of three conditions: local allergic rhinitis (LAR) and local allergic asthma in non-atopic patients, and dual allergic rhinitis (coexistence of allergic rhinitis and LAR) in atopic individuals. LRA is an independent disease phenotype not progressing to atopy over time, but naturally evolving to the clinical worsening and the onset of comorbidities. Published data suggests that LRA is mediated through the mucosal synthesis of allergen-specific (s)IgE, which binds to FcϵRI on resident mast cells, and in >50% of cases traffics to the blood stream to sensitize circulating basophils. To date, 4 clinical trials have demonstrated the capacity of allergen immunotherapy (AIT) to decrease nasal, conjunctival and bronchial symptoms, to improve quality of life, to increase the threshold dose of allergen eliciting respiratory symptoms, and to induce serum sIgG4 in LRA individuals. Collectively, these data indicate that local allergy is a relevant disease mechanisms in both atopic and non-atopic patients with airway diseases.

A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

irway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.

Small airway dysfunction in patients with cough variant asthma: a retrospective cohort study

BackgroundCough variant asthma (CVA) is one of the special populations of asthma. The aim of the study was to compare small airways, the degree of bronchial hyperresponsiveness (BHR) and airway inflammatory subtypes between CVA and classic asthma (CA), and investigate the relationship between these markers to determine the accuracy as indicators of CVA.MethodsA total of 825 asthmatic patients participated in the study and 614 were included. 614 patients underwent spirometry and a bronchial challenge with methacholine and 459 patients performed induction sputum cell test.ResultsThe number of CVA patients showed less small airway dysfunction than those of CA patients (p < 0.005). The degree of small airways dysfunction was higher in the CA group compared with the CVA group (p < 0.001). Small airways dysfunction was severer in the eosinophilic airway inflammatory subtype compared with other subtypes (p < 0.05).The area under curve of MMEF, FEF50 and FEF75 (% predicted) was 0.615, 0.621, 0.606, respectively. 0.17mcg of PD20 and 4.7% of sputum eosinophils was the best diagnostic value for CVA with an AUC of 0.582 and 0.575 (p = 0.001 and p = 0.005, respectively).ConclusionsThe eosinophilic airway inflammatory subtype may be increased small airway dysfunction. The value of small airways, BHR and induction sputum cells in CVA prediction, which reflected significant, but not enough to be clinically useful.

Increased IL-6 and Potential IL-6 trans-signalling in the airways after an allergen challenge.

In asthma, IL-6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL-6 signalling is regulated by its receptor, which is composed of two proteins, IL-6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signalling in cells lacking IL-6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL-6 trans-signalling. We aimed to analyse IL-6 trans-signalling proteins in the airways of subjects after an allergen challenge. We used a model of segmental bronchoprovocation with an allergen (SBP-Ag) in human subjects with allergy. Before and 48h after SBP-Ag, bronchoalveolar lavages (BALs) allowed for the analysis of proteins in BAL fluids (BALFs) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA sequencing (RNA-seq) and used proteomic data to further inform on the expression of the IL-6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL-6 trans-signalling on bronchial fibroblasts, in vitro. IL-6, sIL-6R, sGP130 and the molar ratio of sIL-6R/sGP130 increased in the airways after SBP-Ag, suggesting the potential for enhanced IL-6 trans-signalling activity. BAL lymphocytes, monocytes and eosinophils displayed IL-6R on their surface and were all possible providers of sIL-6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL-6 trans-signalling produced enhanced amounts of the chemokine, MCP-1 (CCL2). After a bronchial allergen challenge, we found augmentation of the elements of IL-6 trans-signalling. Allergen-induced IL-6 trans-signalling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.

BRONCHIAL ASTHMA WITH VOCAL CORD DYSFUNCTION DIFFERENTIATED FROM SEVERE ASTHMA BY BRONCHOSCOPY

Although an important cause of vocal cord dysfunction (VCD) is psychogenic reaction, VCD may be associated with severe asthma and must be distinguished from the disease. A 30-years-old woman was admitted to our hospital with dyspnea despite treatment for asthma. Inspiratory stridor and expiratory wheezes were noted, and neck and chest computed tomography showed normal airways and lungs. Fractional exhaled nitric oxide levels were also normal. Pulmonary function test with a flow-volume loop curve showed normal expiratory loop with flattening of the inspiratory loop after methacholine inhalation. During the attack, bronchoscopy revealed the vocal cord closing with stridor during the inspiratory phase. Therefore, the patient was diagnosed with VCD. The dyspnea improved with respiratory rehabilitation and pursed-lip breathing. VCD should be considered in the differential diagnosis of intractable severe asthma. In this case, bronchoscopy and bronchial inhalation challenge with methacholine helped in the diagnosis.

Association between sensitization and allergic diseases in 7-years-old Korean children.

Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children. We characterized the association between sensitization patterns and allergic diseases. A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Pulmonology approach in the investigation of chronic unexplained dyspnea.

ABSTRACTChronic unexplained dyspnea and exercise intolerance represent common, distressing symptoms in outpatients. Clinical history taking and physical examination are the mainstays for diagnostic evaluation. However, the cause of dyspnea may remain elusive even after comprehensive diagnostic evaluation-basic laboratory analyses; chest imaging; pulmonary function testing; and cardiac testing. At that point (and frequently before), patients are usually referred to a pulmonologist, who is expected to be the main physician to solve this conundrum. In this context, cardiopulmonary exercise testing (CPET), to assess physiological and sensory responses from rest to peak exercise, provides a unique opportunity to unmask the mechanisms of the underlying dyspnea and their interactions with a broad spectrum of disorders. However, CPET is underused in clinical practice, possibly due to operational issues (equipment costs, limited availability, and poor remuneration) and limited medical education regarding the method. To counter the latter shortcoming, we aspire to provide a pragmatic strategy for interpreting CPET results. Clustering findings of exercise response allows the characterization of patterns that permit the clinician to narrow the list of possible diagnoses rather than pinpointing a specific etiology. We present a proposal for a diagnostic workup and some illustrative cases assessed by CPET. Given that airway hyperresponsiveness and pulmonary vascular disorders, which are within the purview of pulmonology, are common causes of chronic unexplained dyspnea, we also aim to describe the role of bronchial challenge tests and the diagnostic reasoning for investigating the pulmonary circulation in this context.

Inflammatory Subtypes in Classic Asthma and Cough Variant Asthma.

BackgroundMeasurement of sputum is used to define airway inflammatory phenotypes. Cough variant asthma (CVA) is considered to be the initial stage of classic asthma (CA). The aim of this study was to describe the association between the different subtypes of CVA and CA.MethodsA total of 459 patients with CVA and CA were screened for the study. All included patients performed spirometry, underwent a bronchial challenge with methacholine and induced sputum according to the guidelines.ResultsA higher frequency of female patients were found with CVA and the eosinophilic airway inflammation of CVA than in CA and the noneosinophilic airway inflammation of CA (p=0.004 and p=0.024, respectively). Bronchial hyper-responsiveness (BHR) was lower in eosinophilic CVA and CA (p=0.006), while no difference was found in noneosinophilic CVA and CA. Association between the percentage of sputum eosinophils and the FEV1 level fell below 20% of the baseline value (PD20) in CVA and CA (r= −0.1245, p=0.0357 and r= −0.2148, p=0.0014, respectively).ConclusionEosinophilia may be associated with more severe disease, yet there was no difference in spirometry between the eosinophilic and noneosinophilic groups, and the BHR difference was not dramatic.

Small Airways Dysfunction and Bronchial Hyper-Responsiveness in Cough Variant Asthma.

BackgroundCough variant asthma (CVA) is one kind of atypical asthma. The study was to compare spirometric parameters of small airways and the degree of bronchial hyper-responsiveness (BHR) between CVA and classic asthma (CA), and examine the relationship between BHR and small airways to determine the accuracy of these markers as indicators of CVA.MethodsA total of 825 asthmatic patients were screened for the study, and 614 were included. All patients performed spirometry and underwent a bronchial challenge with methacholine.ResultsThe number of small airways dysfunctions in the CVA group was less than those of the CA group with MMEF% predicted (70% vs 80.91%, P=0.002) and FEF50% predicted (62.71% vs 73.5%, P=0.004). The degree of small airways dysfunction was less in the CVA group compared with the CA group (P<0.001). Significant positive correlations were observed between the FEV1 level below 20% of the baseline value (PD20) and MMEF% predicted (r=0.282, P<0.001), FEF50% predicted (r=0.2522, P<0.001), and FEF75% predicted (r=0.2504, P<0.001) in patients with CVA. The area under curve (AUC) of MMEF, FEF50, and FEF75 (% predicted) was 0.615, 0.621, and 0.606, respectively. In addition, 0.17 mcg of PD20 was the best diagnostic value for CVA, with an AUC of 0.582 (P=0.001).ConclusionSmall airway dysfunction is milder in CVA. The value of BHR combined with small airways in CVA prediction, which was significant, but not enough to be clinically useful.

Precision Medicine in House Dust Mite-Driven Allergic Asthma.

House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA.

The use of a direct bronchial challenge test in primary care to diagnose asthma

Many asthmatics in primary care have mild symptoms and lack airflow obstruction. If variable expiratory airflow limitation cannot be determined by spirometry or peak expiratory flow, despite a history of respiratory symptoms, a positive bronchial challenge test (BCT) can confirm the diagnosis of asthma. However, BCT is traditionally performed in secondary care. In this observational real-life study, we retrospectively analyze 5-year data of a primary care diagnostic center carrying out BCT by histamine provocation. In total, 998 primary care patients aged ≥16 years underwent BCT, without any adverse events reported. To explore diagnostic accuracy, we examine 584 patients with a high pretest probability of asthma. Fifty-seven percent of these patients have a positive BCT result and can be accurately diagnosed with asthma. Our real-life data show BCT is safe and feasible in a suitably equipped primary care diagnostic center. Furthermore, it could potentially reduce diagnostic referrals to secondary care.

Methacholine-induced cough as an indicator of bronchodilator-responsive cough

BackgroundCough variant asthma (CVA) is the most common cause of chronic cough and responds well to bronchodilator therapy. Previous studies on methacholine -induced cough have shown that heightened cough response due to bronchoconstriction is a feature of CVA. The aim of this study was to assess Mch-induced cough as an indicator of bronchodilator-responsive cough (BRC). MethodsThis was a single-center retrospective study of prolonged/chronic cough cases who underwent evaluation via spirometry, FeNO and bronchial challenge testing using Mch and capsaicin (C5). Resultant bronchoconstriction after Mch challenge was assessed by flow-volume curves measuring the expiratory flow of the partial flow-volume curve 40% above residual volume (PEF40) and FEV1. BRC was defined as a decrease in cough with bronchodilator therapy by 30% or more on a visual analog scoring scale. ResultsOf the 100 patients evaluated, 63 were diagnosed with BRC. Mch-induced cough at a decrease in PEF40 of 35% (PC35-PEF40) was predictive of BRC on AUROC analysis with an AUC of 0.82 (95% CI 0.73–0.90) and cut-off of 24. The AUC for C5, FeNO and PC20-FEV1 were 0.65, 0.47, and 0.58, respectively. ConclusionCompared to C5, FeNO and PC20-FEV1, Mch-induced cough better supports a diagnosis of BRC.

Questionnaires or Serum Immunoglobulin G Testing in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease.

Rationale: Hypersensitivity pneumonitis (HP) results from exposure to a variety of stimuli, which are challenging to identify. Questionnaires and serum immunoglobulin G (IgG) testing are methods to identify potentially causative exposures.Objectives: To perform a systematic review to determine the usefulness of questionnaires and serum IgG testing in identifying exposures that may have caused HP.Methods: This systematic review informed an international, multidisciplinary panel that developed a clinical practice guideline on the diagnosis of HP for the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax. MEDLINE, the Cochrane Library, and EMBASE were searched from January 1946 to October 2019 for studies that used a questionnaire or serum IgG testing to identify exposures that may have caused HP. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of the evidence.Results: Searches identified 1,141 and 926 potentially relevant articles for questionnaires and serum IgG testing, respectively. The full texts of 32 and 49 articles, respectively, were reviewed. Two observational studies for questionnaires and 15 accuracy studies for serum IgG testing were selected. Questionnaires were better at detecting potentially relevant exposures than clinical history (100% vs. 26%; risk ratio [RR], 3.80; 95% confidence interval [95% CI], 1.79-8.06) and serum IgG testing (100% vs. 63%; RR, 1.58; 95% CI, 1.12-2.23) but did not differ from serum IgG testing plus bronchial challenge testing (59% vs. 65%; RR, 0.90; 95% CI, 0.65-1.24). Longer, detailed questionnaires were more likely to lead to identification of potential exposures. Only 70% of potential exposures identified by questionnaires were subsequently confirmed by environmental testing. Serum IgG testing distinguished HP from healthy exposed and unexposed control subjects with high sensitivity (90% and 92%, respectively) and high specificity (91% and 100%, respectively) but did not distinguish HP as effectively from interstitial lung diseases (ILDs; sensitivity of 83% and specificity of 68%).Conclusions: Using a questionnaire may help clinicians identify potentially relevant exposures when evaluating a patient with newly identified ILD for HP. Serum IgG testing may also lead to identification of potentially relevant exposures, but its usefulness for distinguishing HP from other types of ILD is poor.

Occupational airborne contact urticaria, anaphylaxis and asthma in farmers and agronomists due to Bruchus pisorum.

Occupational contact urticaria due to inhalation of legume pest allergens has rarely been described. To determine the cause of an outbreak of airborne contact urticaria, asthma, and anaphylaxis in farmers and agronomists studying the disinsectization of dried peas. Peas were treated with aluminum phosphide (EPA). Extracts prepared from Bruchus lentis and Bruchus pisorum bodies and from healthy legumes, EPA-treated legumes, and infested legumes, were used for in vivo tests (skin prick testing, oral, and specific bronchial challenge for the diagnosis of asthma and anaphylaxis) in affected patients and in five control patients with severe legume hypersensitivity. Open application, patch testing with the most common legume insecticides, molecular analysis, and IgE immunoblotting were undertaken. We found positive responses (prick, provocation, immune detection) to parasitic pea extracts and B. pisorum. A 25 kDa band was detected in the western blot of all patients who worked with infested EPA-treated peas. Bands from B. pisorum extract were detected in all patients. No responses to pea allergens were found in any patient, unlike in legume allergy controls. Oral provocation tests were negative. B. pisorum is a cause of contact urticaria and may cause occupational hives, anaphylaxis, and asthma. The allergen may enter by inhalation or puncture of setae released by B. pisorum.

Bronchial challenge test in patients with a history suggestive of bronchial asthma with normal spirometric studies

BackgroundBronchial hyper-responsiveness (BHR) is the hallmark of bronchial asthma, characterized by clinical features of cough, wheeze, breathlessness and chest tightness which are confirmed by spirometry showing obstructive pattern and reversibility to bronchodilators. In individuals having features of bronchial asthma but normal spirometry, demonstration of BHR with bronchial challenge test (direct or indirect) confirms/ rules out the diagnosis. The aim of this study was to assess BHR in patients (methacholine challenge) with a history suggestive of bronchial asthma but normal spirometry and its role in diagnosis of bronchial asthma. MethodsThis study was conducted at tertiary care respiratory center. Patients having clinical features of bronchial asthma but spirometry not confirming obstructive disorder and or reversibility were included in the study. After written consent, methacholine challenge test with methacholine chloride and exercise spirometry was done in all patients as per the American Thoracic Society protocol. ResultsA total of 50 (n) patients were included in the study. Among them, 42 patients had clinical features suggestive of bronchial asthma but having normal spirometry and eight patients were diagnosed as they had bronchial asthma in the past but asymptomatic and off drugs were included in the study. At PC20 4mg/ml 32 (64%) patients had a positive test, 28(66%) symptomatic patients and four (50%) asymptomatic asthmatics. There were no significant side effects with methacholine test. ConclusionAirway hyper-responsiveness is an important aspect of bronchial asthma and its demonstration with bronchial challenge (direct and indirect) test is an important diagnostic tool. Methacholine challenge test is a safe procedure to perform under supervision.

Different Development Forms of Local Allergic Rhinitis towards Birch.

Background Efficacy of allergen immunotherapy (AIT) in local allergic rhinitis (LAR) is a new subject of research. The presence of asthmatic symptoms in patients with LAR in the context of AIT is unexplored. Objective The efficacy and safety of AIT in patients with LAR towards birch pollen were investigated. The possibility of concomitant local allergic asthma in studied patients and the impact of AIT on it were examined. Methods 36 patients with LAR towards birch were included in three years of AIT in a double-blind, placebo-control study. Primary outcome measurement was the mean changes in the combined symptom and medication scores (CSMSs) after AIT, and the second is the changes in the quality of life (QoL). Skin prick tests, serum, nasal allergen-specific IgE to birch, nasal and bronchial provocation challenge tests with birch allergen, methacholine tests, and spirometry were carried out at baseline and after AIT. Results Mean CSMSs of three years of AIT were significantly decreased in the active group from 5.88 (range: 4.11-9.01) to 1.98 (range: 1.22-4.51; p < 0.05). After three years of AIT, there was a significant increase of toleration for birch allergen from the mean concentration of 6250 ± 1200 SQ-U/ml up to 45000 ± 2500 SQ-U/ml (p = 0.02) during repeated nasal challenges. 16 patients with LAR had the positive results of methacholine tests, and 11 of them had a positive bronchial challenge to birch allergen. After AIT, the significant decrease of bronchial responsiveness to birch allergen in 5 from 7 patients was confirmed (p = 0.03). QoL assessed by the use of the RQLQ score was improved after AIT from 1.84 (95% CI: 1.53-1.97) to 1.45 (95% CI: 1.32-1.62) score in the active group after three years of AIT therapy (p = 0.03). Conclusion AIT to birch can be useful and safe in a patient with local allergic rhinitis and also with concomitant asthmatic symptoms. Further studies are needed.

Characterising the role of small airways in severe asthma using low frequency forced oscillations: A combined computational and clinical approach.

Within asthma, the small airways (≤2mm in diameter) play an important role in pathophysiology. Using a combined clinical-computational approach, we sought to more precisely evaluate the contribution of the small airways to deep-breath induced airway dilation (in the absence of bronchial challenge), which may be impaired in severe asthma. A patient-based computational model of the FOT was used to examine the sensitivity and specificity of FOT signals to small airways constriction at frequencies of 2 & 8Hz. A clinical study of moderate to severe asthmatics (n=24), and healthy volunteers (n=10) was performed to evaluate correlations between baseline and post deep inspiration (following bronchodilator withhold and in the absence of prior bronchial challenge) forced oscillation technique (FOT) responses (at 2Hz and 8Hz) and asthma treatment intensity, spirometry, airway hyper-responsiveness and airway inflammation. Computational modelling demonstrated that baseline resistance measures at 2Hz are both sensitive and specific to anatomical narrowing in the small airways. Furthermore, small airways resistance was significantly increased in asthmatics compared to health. Despite these differences, there were no noticeable differences between asthmatics and healthy volunteers in resistive measures following deep inspiration (DI) and DI responses of small airways were amplified in the presence of spirometry defined airflow limitation. These results suggest that the small airways demonstrate increased resistance in moderate-to-severe asthma but dilate normally in response to deep inspirations in the absence of bronchial challenge. This suggests that effective targeting of the small airways is required to achieve functional improvements in moderate-severe asthmatic patients.

Predictive value of non-specific bronchial challenge testing for respiratory symptoms and lung function in aluminium smelter workers

ObjectiveTo assess the predictive value of bronchial hyper-responsiveness (BHR) for the subsequent development of respiratory symptoms, airflow limitation and decline in lung function among aluminium smelter workers.MethodsAn inception cohort study...