Exacerbations Among Patients With Asthma Are Largely Dependent on the Presence of Multimorbidity.

BACKGROUND AND OBJECTIVE: Comorbidities can influence asthma control and promote asthma exacerbations (AEs). However, the impact of multimorbidity in AEs, assessed based on long-term follow-up of patients with asthma of different degrees of severity, has received little attention in real-life conditions. To describe the epidemiological and clinical characteristics and predictors of AEs in patients who had presented at least 1 AE in the previous year in the MEchanism of Genesis and Evolution of Asthma (MEGA) cohort. METHODS: The work-up included a detailed clinical examination, pulmonary function testing, fractional exhaled nitric oxide (FeNO), blood counts, induced sputum, skin prick-tests, asthma questionnaires, and assessment of multimorbidity. The number of moderate-severe AEs in the preceding year was registered for each patient. RESULTS: The study population comprised 486 patients with asthma (23.7% mild, 35% moderate, 41.3% severe). Disease remained uncontrolled in 41.9%, and 47.3% presented ≥1 moderate-severe AE, with a mean (SD) annual exacerbation rate of 0.47 (0.91) vs 2.11 (2.82) in mild and severe asthma, respectively. Comorbidity was detected in 56.4% (66.6% among those with severe asthma). Bronchiectasis, chronic rhinosinusitis with nasal polyps, atopy, psychiatric illnesses, hyperlipidemia, and hypertension were significantly associated with AEs. No associations were found for FeNO, blood eosinophils, or total serum IgE. Sputum eosinophilia and a high-T2 inflammatory pattern were significantly associated with AEs. Multivariable regression analysis showed a significant association with asthma severity, uncontrolled disease, and low prebronchodilator FEV1/FVC. CONCLUSION: Our study revealed a high frequency of AE in the MEGA cohort. This was strongly associated with multimorbidity, asthma severity, poor asthma control, airflow obstruction, higher sputum eosinophils, and a very high-T2 inflammatory pattern.

A case of self-improving collodion ichthyosis associated with a rare variant of the ALOX12B gene.

Collodion baby is usually a manifestation of autosomal recessive congenital ichthyosis, a heterogeneous group of congenital hyperkeratotic genodermatoses with highly variable severity and genetic background. Herein, we report a case of self-improving collodion ichthyosis, a rare subtype of autosomal recessive congenital ichthyosis, characterized by an almost-complete spontaneous resolution of symptoms.

Role of diesel exhaust particles in the induction of allergic asthma to low doses of soybean.

INTRODUCTION: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of asthma and asthma exacerbation. However, the exact mechanisms inducing asthma to low doses of allergens remain poorly understood. The present study aimed to analyse the immunomodulatory effect of the inhalation of DEP in a mouse model exposed to non-asthmagenic doses of soybean hull extract (SHE). MATERIAL AND METHODS: BALB/c ByJ mice were randomly divided into four experimental groups. Two groups received nasal instillations of saline and the other two groups received 3 mg ml-1 SHE during 5 days per week for 3 weeks. One group in each pair also received 150 µg of DEP in the same instillations 3 days per week. SHE-specific IgE levels, oxidative stress, leukocyte pattern and optical projection tomography (OPT) imaging studies were assessed. RESULTS: Inhalation of SHE and/or DEP increased levels of H2O2 in BAL, while coexposure to SHE and DEP increased SHE-specific IgE levels in serum. Inhalation of SHE alone increased eosinophils, B cells, total and resident monocytes and decreased levels of NK cells, while inhalation of DEP increased neutrophils and decreased total monocytes. Regarding dendritic cells (DC), the inhalation of SHE and/or DEP increased the total population, while the inhalation of SHE alone increased Th2-related DCs (CD11b + Ly6C-) and decreased tolerogenic DCs (CD11b-Ly6C-). However, coexposure to SHE and DEP increased oxidative stress-sensitive DCs (CD11b-Ly6C+) and decreased Th1-related DCs (CD11b + Ly6C+). As regards macrophages, inhalation of SHE and DEP decreased total and alveolar populations. DEP deposition in lung tissue did not differ between groups. CONCLUSION: Coexposure to DEP activates the asthmatic response to low doses of soy by triggering the immune response and oxidative stress.

Immunomodulatory effect of pigeon serum in an acute and chronic murine model of bird fanciers lung.

INTRODUCTION: Since the immunopathological mechanisms of bird fancier's lung (BFL) are not well known, we created two models of the disease (acute and chronic BFL) to study and compare the pathways involved in its immunopathogenesis. MATERIALS AND METHODS: C57BL/6 mice were used. Two intraperitoneal injections of 100 µL of commercial pigeon serum (PS) or saline (SAL) were administered with an interval of 48 h in between. Subsequently, intranasal instillations of 40 µL of PS or SAL were performed three days a week, for three weeks in the acute model (AC/PS) and for twelve weeks in the chronic model (CR/PS). Total lung capacity (TLC) was assessed. Pulmonary inflammation was evaluated in bronchoalveolar lavage (BAL), and total serum immunoglobulin (Ig) G was measured in serum samples 24 h, 7 days and 14 days after the last exposure. Histological studies of lungs were assessed. RESULTS: A drop in TLC was observed in treated mice. This decrease was more marked in the CR/PS group (p < 0.001). Neutrophil and lymphocyte counts increased in both AC/PS and CR/PS groups (p < 0.01). The extent of airway inflammation was also examined in the histological analysis of the lungs, which showed predominant perivascular and peribronchiolar inflammation, with centrilobular oedema and subpleural inflammation in the AC/PS group. In the CR/PS group, the changes were greater, with increased levels of IL-5, IL-17F, IL-13 and IL-10 and decreased levels of IL-2. CONCLUSIONS: Bronchial inflammation is present in acute and chronic models of HP following exposure to PS. Our results support the role of neutrophils and IL-17 in the development of the disease and an evolution towards a Th-2 immune response in chronic HP. These models may serve as a tool for future studies of the pathogenesis of HP.

Suspension Training HIIT Improves Gait Speed, Strength and Quality of Life in Older Adults.

This study aimed to evaluate the effects of a 12-week high-intensity interval exercise (HIIT) training program involving suspension exercises (TRX) on the muscle strength, body composition, gait speed, and quality of life of older adults. A total of 82 older adults were randomly assigned to 3 groups: a HIIT group (n=28), a continuous intensity training group (MIIT group, n=27), or a control group (CG, n=27). Compared to MIIT and CG, participants of the HIIT group showed significant post-intervention improvements in BMI (p=.002 and p<.001, respectively) and gait speed (p<.001 for both). Handgrip strength increase was also observed after HIIT (p=.002), but no differences were observed with MIIT and CG. Compared with MIIT and control groups, HIIT showed improvements in the SF-36 domains: general health (p<.001 for both) health changes (p<.001 for both), vitality (p=.002 and p=.001 respectively) and physical functioning (p=.036 and p<.001 respectively). Our results suggest that a HIIT training program with TRX have benefits in BMI, handgrip strength, gait speed, and quality of life in older adults.

Expansion of a CD26low Effector TH Subset and Reduction in Circulating Levels of sCD26 in Stable Allergic Asthma in Adults.

BACKGROUND AND OBJETIVE: The pathogenesis of asthma is dependent on the balance between regulatory and effector T cells, which display differential expression of CD25 and CD26. Therefore, alteration of circulating levels of sCD25 and sCD26 during allergic asthma could be conditioned by changes in leukocyte phenotype. Objectives: To analyze expression of CD25 and CD26 on T lymphocytes and their soluble derivatives (sCD25, sCD26) during stable phases of moderate-severe allergic asthma. METHODS: Cross-sectional study with 2 adult cohorts of allergic asthmatics. Clinical, anthropometric, pulmonary, hematological, and biochemical parameters were measured. Phenotyping was performed with flow cytometry in both circulating and cultured leukocytes. Dipeptidyl peptidase 4 (DPP4) activity was assayed in culture supernatants. RESULTS: In vitro studies revealed upregulation of CD26 on human T lymphocytes upon activation, especially under TH17-favoring conditions, and a correlation with soluble DPP4 activity (rs=0.641; P<.001). CD26 expression on lymphocytes was higher in asthmatics, while serum sCD26 was lower in women and patients. The latter finding could be associated with an expanded CD25low/CD26low/CD127low subset of effector CD4+ T cells in allergic asthma, with no changes in Treg percentages. However, women showed an increased Teff/Treg ratio, which could explain their greater susceptibility to asthma. CONCLUSIONS: Allergic asthma causes an increment in CD25lowCD26low helper T cells detected in stable stages. These changes are mirrored in serum and should be considered in the light of the downmodulating role of CD26 in major chemokines related to the pathogenesis of asthma such as CCL11 (eotaxin), CCL5 (RANTES), and CXCL12a (SDF-1α).

Effect of anti-IgE in occupational asthma caused by exposure to low molecular weight agents.

BACKGROUND: The role of immunoglobulin (Ig)-E in occupational asthma (OA) due to low molecular weight (LMW) agents is not well established compared to classical atopic asthma. In this study, we evaluate whether anti-IgE monoclonal antibody (mAb) has an effect in a mouse model of OA, using persulfate salts. METHODS: On days 1 and 8, BALB/C mice were dermally sensitized with 5% ammonium persulfate (AP) or dimethyl sulfoxide (DMSO). On days 15, 18, and 21, animals were injected intraperitoneally with anti-IgE mAb or PBS 6 hours before challenge with AP or saline. Airway hyper-responsiveness (AHR) using a methacholine test, airway inflammation in bronchoalveolar lavage (BAL) and lung tissue, and total free IgE in serum samples were analyzed 24, 48, and 96 hours after the last challenge. RESULTS: Anti-IgE mAb treatment almost completely neutralized free serum IgE. In AP-sensitized and challenged mice, anti-IgE mAb treatment abolished AHR 24 hour and 48 hour after the last challenge and significantly reduced the total number of eosinophils and neutrophils 48 hour and 96 hour after the last AP challenge compared with nontreated mice. Levels of interleukin (IL)-13 in BAL were also significantly decreased after anti-IgE administration 24 hour and 48 hour after the last AP challenge. Histological analysis of the lung sections from anti-IgE-treated mice revealed normal inflammatory patterns similar to control groups 48 hour after the last challenge. CONCLUSIONS: Anti-IgE-treated mice showed a significant improvement in asthma features related to the AHR and airway inflammation. Anti-IgE mAb has positive effects in OA induced by persulfate salts.

First Identification of Pulmonary Asbestos Fibres in a Spanish Population.

INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations. MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm. CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.

Cross-sectional study about impact of parental smoking on rhinitis symptoms in children.

OBJECTIVE: Assess the prevalence of rhinitis and exposure to environmental tobacco smoke (ETS) of children in our community and its relationship with symptoms of rhinitis METHODS (DESIGN, SETTING, PARTICIPANTS, MAIN OUTCOME MEASURES): Cross-sectional study using questionnaire on rhinitis of the International Study of Asthma and Allergies in Childhood, in children (6-7 years) and adolescents (13-14 years). Categories: "rhinitis ever", "recent rhinitis", "recent rhinoconjunctivitis", "severe rhinoconjunctivitis". Parental smoking: (i) neither parent smokes; (ii) only the mother smokes; (iii) only the father smokes; and (iv) both parents smoke. Odds ratio of the prevalence of symptoms of rhinitis according to ETS exposure was calculated using logistic regression. RESULTS: 10 690 children and 10 730 adolescents. The prevalence of "rhinitis ever" in children: 29.4%, "recent rhinitis" 24%, "recent rhinoconjunctivitis" 11.5% and "severe rhinoconjunctivitis" 0.1%. In adolescents: 46.2%, 34.5%, 16.2% and 0.2%, respectively. Environmental tobacco smoke exposure in the home occurred in 51% of cases. Parental smoking was associated with a higher prevalence of forms of rhinitis in adolescents when only the mother was a smoker. In children when both parents were smokers. CONCLUSION: Rhinitis is highly prevalent in our community. Environmental tobacco smoke exposure is still very common. The relationship between ETS and rhinitis symptoms in children of this community is not as robust as that found for asthma.

Occupational hypersensitivity pneumonitis: an EAACI position paper.

The aim of this document was to provide a critical review of the current knowledge on hypersensitivity pneumonitis caused by the occupational environment and to propose practical guidance for the diagnosis and management of this condition. Occupational hypersensitivity pneumonitis (OHP) is an immunologic lung disease resulting from lymphocytic and frequently granulomatous inflammation of the peripheral airways, alveoli, and surrounding interstitial tissue which develops as the result of a non-IgE-mediated allergic reaction to a variety of organic materials or low molecular weight agents that are present in the workplace. The offending agents can be classified into six broad categories that include bacteria, fungi, animal proteins, plant proteins, low molecular weight chemicals, and metals. The diagnosis of OHP requires a multidisciplinary approach and relies on a combination of diagnostic tests to ascertain the work relatedness of the disease. Both the clinical and the occupational history are keys to the diagnosis and often will lead to the initial suspicion. Diagnostic criteria adapted to OHP are proposed. The cornerstone of treatment is early removal from exposure to the eliciting antigen, although the disease may show an adverse outcome even after avoidance of exposure to the causal agent.

Utility of Exhaled Nitric Oxide Fraction for the Diagnosis of Hypersensitivity Pneumonitis.

BACKGROUND: There is very little evidence of the utility of the exhaled fraction of NO (FeNO) for the diagnosis of interstitial lung disease and nearly all of it is related with connective tissue disease. Some authors have suggested that in patients with hypersensitivity pneumonitis (HP), evolution to pulmonary fibrosis may be mediated by a Th2 mechanism, which could redound in a potential utility of FeNO. The aim of this study was to investigate the values of FeNO before and after antigenic exposure with the specific inhalation challenge (SIC) and to analyze its potential utility for the diagnosis of HP. METHODS: It was a prospective, cross-sectional study of all patients older than 18 years referred to our center for suspected chronic HP between May 2012 and May 2014 and who underwent a SIC. FeNO was collected before and after SIC. RESULTS: The study sample comprised 25 patients. Eleven were diagnosed with chronic HP; six had been exposed to avian proteins and five to fungal agents. Of these 11 patients, seven had positive SICs. In the 14 patients with diagnoses other than HP, all the SICs were negative. No significant differences in baseline characteristics were observed according to HP diagnosis, except in the BAL lymphocyte count. No differences were found after the test in patients diagnosed with HP; nor were there differences in baseline FeNO in patients diagnosed with HP and those who received alternative diagnoses. CONCLUSIONS: The results suggest that FeNO measurement is not useful for the diagnosis of chronic HP.

Changes in PH in exhaled breath condensate after specific bronchial challenge test in patients with chronic hypersensitivity pneumonitis: a prospective study.

BACKGROUND: The aim of this study was to investigate the influence of the specific inhalation challenge (SIC) on changes of pH values in exhaled breath condensate (EBC) in patients with hypersensitivity pneumonitis (HP). METHODS: A prospective study of 85 patients with suspected HP, of whom 63 were diagnosed with HP due to exposure to avian or fungal antigens. In all cases, EBC samples were collected before and after completion of the SIC and pH values were determined. RESULTS: Taken as a whole, patients with HP did not present changes in EBC pH after SIC. However, considering only patients with exposure to molds, those diagnosed with HP had a significantly more acid pH post-SIC than those with another diagnosis (p = 0.011). This fact is not observed in patients exposed to bird's antigens. A ROC curve showed that a reduction in EBC pH of 0.3 units or more after SIC in patients diagnosed with HP due to exposure to molds had a sensitivity of 30 % (CI: 12.8 to 54.3 %) and a specificity of 100 % (CI: 65.5 to 100 %). CONCLUSION: EBC pH may be useful in interpreting SIC results in patients with HP, especially in those patients exposed to molds. Further studies are now required to test the validity of these proposals.

Work-related asthma: diagnosis and prognosis of immunological occupational asthma and work-exacerbated asthma.

The incidence and prevalence of asthma are increasing. One reason for this trend is the rise in adult-onset asthma, especially occupational asthma, which is 1 of the 2 forms of work-related asthma. Occupational asthma is defined as asthma caused by agents that are present exclusively in the workplace. The presence of pre-existing asthma does not rule out the possibility of developing occupational asthma. A distinction has traditionally been made between immunological occupational asthma (whether IgE-mediated or not) and nonimmunological occupational asthma caused by irritants, the most characteristic example of which is reactive airway dysfunction syndrome. The other form of work-related asthma is known as work-exacerbated asthma, which affects persons with pre-existing or concurrent asthma that is worsened by work-related factors. It is important to differentiate between the 2 entities because their treatment, prognosis, and medical and social repercussions can differ widely. In this review, we discuss diagnostic methods, treatment, and avoidance/nonavoidance of the antigen in immunological occupational asthma and work-exacerbated asthma. Key words: Specific inhalation challenge. Peak expiratory flow. Workplace. Irritants.

Soy aeroallergens in thoracic fraction particles (PM10).

BACKGROUND: The aerodynamic diameter of biological particles determines their ability to penetrate the human respiratory system. OBJECTIVE: To assess the content of allergens less than 10 pm in diameter in the particle fraction of airborne dust in order to improve control of exposure to harmful soybean aeroallergens. METHODS: In this study, 98 pairs of particulate matter measuring less than 10 microm in diameter (PM10) and total suspended particulate (TSP) filters were collected in parallel and analyzed for soy aeroallergens by the inhibition enzyme-linked immunosorbent assay. RESULTS: The median levels found were 6 and 22.5 U/m3 for PM10 and TSP filters, respectively. A good correlation was found between soy aeroallergen content in PM10 and TSP filters. The median proportion of soy aeroallergen content in PM10 filters versusTSP filters was 28.6%, and varied widely across different days. CONCLUSIONS: Due to this wide variation between days, it seems that soy aeroallergen content in TSP filters is not a good surrogate of soy allergen content in PM10 filters. Further clinical studies should be conducted to assess differences in the health impact of soy allergen content in PM10 filters and TSP filters.

Adherence of five serovars of Ornithobacterium rhinotracheale to chicken tracheal epithelial cells.

1. Interaction between bacteria and host tissue is important, both for primary adhesion and tissue-specific colonisation, as well as for pathogen invasion for different host tissues. 2. Ornithobacterium rhinotracheale is a bacterium associated with respiratory tract infections in poultry. The mechanisms by which O. rhinotracheale causes infection are not known. To date, at least 18 serovars of this bacterium, with or without the ability to agglutinate erythrocytes of chicken and other species, have been identified. 3. The purpose of this work was to evaluate the ability of five references strains, belonging to serovars A, B, C, D and E, to adhere to a culture of primary chicken tracheal cells. 4. Serovars A and B adhered to less than 20% of tracheal cells with no specific adherence pattern. Serovars C, D and E gave adherence values greater than 70%. Serovars C and E showed a diffuse adherence pattern, while serovar D had an aggregated adherence pattern. 5. The adherence ability and pattern could be associated with different pathogenicity mechanisms in the various serovars but more studies are needed to understand the reasons for these differences.

Bronchial inflammation and hyperresponsiveness in well controlled asthma.

BACKGROUND: Little research has been devoted to the characteristics of bronchial inflammation in patients with stable, well controlled asthma. OBJECTIVE: The aim of this study was to assess the degree and type of airway inflammation and to investigate the relationship between inflammation and bronchial hyperresponsiveness in patients with well controlled asthma. METHODS: A cross-sectional study was conducted in 84 adult patients (43 men, mean age 43 years) with documented well controlled asthma. Induced sputum samples were obtained and cell types determined by differential cell count. Spirometry and methacholine challenge testing were performed. Asthma Control Questionnaire (ACQ) was used to assess symptoms. Patients were included if their ACQ score was < 0.75. RESULTS: A total of 59 patients had persistent bronchial inflammation: 28 cases were considered eosinophilic, 28 neutrophilic, and 3 mixed. Median (range) percentage of eosinophils was 4% (0-64) in patients testing positive to methacholine challenge (n = 66) and 1% (0-3) in those testing negative (n = 18) (P = 0.003). A positive correlation was found between eosinophil percentage and the methacholine dose/response ratio (r = 0.477, P = 0.0001). The geometric mean (95% CI) of the methacholine PC20 was 1.74 mg/mL (1.04-2.93) in patients with eosinophilic inflammation and 4.14 mg/mL (2.5-6.84) in those with neutrophilic inflammation (P = 0.03). CONCLUSIONS: Inflammation and bronchial hyperresponsiveness persist in most patients with well controlled asthma. CLINICAL RELEVANCE: The study demonstrates that eosinophilic or neutrophilic inflammation persisted in most well controlled asthma patients despite the fact that their condition was controlled and therefore, measurement of bronchial inflammation seems essential to achieve proper asthma control.

Utility of exhaled breath condensate pH for diagnosing occupational asthma.

INTRODUCTION: The current reference standard method for diagnosing occupational asthma (OA) is specific inhalation challenge (SIC) with the suspected agent. The alternative method is serial peak expiratory flow (PEF) monitoring. Nevertheless, PEF does not have optimal sensitivity and specificity for this purpose. The aim of this study was to evaluate the utility of exhaled breath condensate (EBC) pH for the diagnosis of OA. MATERIAL AND METHODS: A prospective study was performed in 37 subjects with suspected OA. Serial PEF monitoring was carried out for 2 weeks at work and for 2 weeks off work. At the end of each period, the EBC pH and the methacholine concentration resulting in a 20% FEV(1) decrease (PC20) were measured. SIC was subsequently performed. PEF graphs were interpreted visually by 3 experienced independent readers. RESULTS: Seventeen patients tested positive with SIC. Receiver-operating characteristic curves showed that a decrease in EBC pH greater than 0.4 units during the period at work compared to the off-work period achieved the most satisfactory sensitivity (40%, CI 19.4-66.5) and specificity (90%, CI 66.9-98.2) for diagnosing OA. When EBC pH findings were added to PEF results, the diagnostic yield of PEF generally increased. Other test combinations (e.g. EBC pH plus PC20 or EBC pH plus PC20 plus PEF) did not improve diagnostic performance. CONCLUSIONS: Acidification of EBC pH at work and adding the EBC pH measurement to PEF monitoring during periods at work and off work may be useful for improving the diagnosis of OA.