PURPOSE: Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma. METHODS: Mycobacterium bovis bacille Calmette-Guerin (BCG; 2x105 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 microg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 microm), and cytokine levels in splenocyte supernatants, were assessed. RESULTS: BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values (P<0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also (P<0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing (P<0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-gamma/IL-5 ratios were significantly higher in mice treated with BCG, 4 microg MPB70 or 4 microg 38-kDa protein than in asthma control mice (P<0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). IL-17A was positively correlated with IL-5 (r=0.379, P<0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). CONCLUSIONS: Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-gamma/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.
Animals ; Asthma ; Bronchi ; Bronchoalveolar Lavage Fluid ; Cell Count ; Eosinophils ; Female ; Goblet Cells ; Humans ; Indoles ; Interleukin-17 ; Interleukin-5 ; Methacholine Chloride ; Mice ; Mycobacterium bovis ; Proteins ; Tuberculosis

PURPOSE: Recent studies have reported that Asian sand dust (ASD) has a potential risk of aggravating airway inflammation. The purpose of this study was to investigate the effect of ASD on inflammation and mucin production in the airways of allergic mice. METHODS: Forty BALB/c female mice were divided into four groups: saline (group 1); ASD (group 2); ovalbumin (OVA) alone (group 3); and OVA+ASD (group 4). OVA-specific immunoglobulin E (IgE) in serum and interleukin (IL)-4, IL-5, IL-13, and interferon-gamma (IFN-gamma) in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Hematoxylin & eosin (H&E) and Periodic acid-Schiff (PAS) staining was performed on lung tissues. In addition, immunohistochemical staining for IL-4, IL-5, MUC5AC, and transforming growth factor alpha (TGF-alpha) was conducted. RESULTS: Serum IgE levels were significantly higher in group 4 than in group 3 (P<0.05). IL-4 and IL-5 in BALF were significantly higher in group 4 than in group 3 (P<0.05, respectively). Based on H&E staining, inflammatory cell numbers were significantly greater in group 4 than in the other groups (P<0.05). The number of PAS-positive cells was also significantly greater in groups 3 and 4 than in groups 1 and 2 (P<0.05). The numbers of IL-4 and IL-5-positive cells were higher in group 4 than in group 3 (P<0.05). The number of MUC5AC and TGF-alpha-positive cells were also higher in group 4 than in group 3 (P<0.05). CONCLUSIONS: Our data suggest that ASD increases cytokine expression and mucin production in an allergic murine model. The increased inflammatory reactions were related to cytokine production.
Animals ; Asian Continental Ancestry Group ; Bronchoalveolar Lavage Fluid ; Cell Count ; Dust ; Enzyme-Linked Immunosorbent Assay ; Eosine Yellowish-(YS) ; Female ; Hematoxylin ; Humans ; Immunoglobulin E ; Immunoglobulins ; Inflammation ; Interferon-gamma ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Interleukins ; Lung ; Mice ; Mucins ; Ovalbumin ; Silicon Dioxide ; Transforming Growth Factor alpha

PURPOSE: The human WD repeat-containing protein 46 (WDR46; also known as C6orf11), located at the disease-relevant centromere side of the class II major histocompatibility complex region, is hypothesized to be associated with risk of aspirin-exacerbated respiratory disease (AERD) as well as a decline in forced expiratory volume in the first second (FEV1), an important diagnostic marker of asthma. METHODS: To investigate the association between WDR46 and AERD, five single-nucleotide polymorphisms (SNPs) were genotyped in 93 AERD cases and 96 aspirin-tolerant asthma controls of Korean ethnicity. Three major haplotypes were inferred from pairwise comparison of the SNPs, and one was included in the association analysis. Differences in the frequency distribution of WDR46 SNPs and haplotype were analyzed using logistic and regression models via various modes of genetic inheritance. RESULTS: Depending on the genetic model, the logistic and regression analyses revealed significant associations between rs463260, rs446735, rs455567, rs469064, and WDR46_ht2 and the risk of AERD (P=0.007-0.04, Pcorr=0.01-0.04) and FEV1 decline after aspirin provocation (P=0.006-0.03, Pcorr=0.01-0.03). Furthermore, functional analysis in silico showed that the G>A allele of rs463260 located in the 5' untranslated region potentially matched a nucleotide sequence within an upstream open reading frame of WDR46. CONCLUSIONS: These findings show for the first time that WDR46 is an important genetic marker of aspirin-induced airway inflammation and may be useful for formulating new disease-management strategies.
5' Untranslated Regions ; Alleles ; Aspirin ; Asthma ; Base Sequence ; Centromere ; Computer Simulation ; Forced Expiratory Volume ; Genetic Markers ; Haplotypes ; Humans ; Inflammation ; Major Histocompatibility Complex ; Models, Genetic ; Open Reading Frames ; Polymorphism, Single Nucleotide ; Risk Factors

PURPOSE: Exercise-induced bronchoconstriction (EIB) in patients with asthma occurs more frequently in winter than in summer. The concentration of house dust mite (HDM) allergens in beds also shows seasonal variation. This study examined the relationship between seasonal differences in the prevalence of EIB and sensitization to HDMs in patients with asthma. METHODS: The medical records of 74 young adult male patients with asthma-like symptoms who underwent bronchial challenge with methacholine, 4.5% saline and exercise, and allergen skin prick tests, were reviewed. The subjects were divided into summer (n=27), spring/fall (n=26) and winter (n=21) groups according to the season during which they underwent testing. RESULTS: The positive responses to exercise differed according to season (48.1% in summer, 73.1% in spring/fall, and 90.5% in winter; P<0.01). In addition, the prevalence of positive responses to HDM (70.4%, 88.5%, and 95.2%, respectively; P<0.05) and pollen skin tests (37.0%, 19.2%, and 0%, respectively; P<0.01) also showed significant seasonal differences. Severe responses to 4.5% saline showed a similar trend, although it was not statistically significant (44.4%, 50.0%, and 71.4%, respectively; P=0.07). Skin test reactivity to HDMs was significantly related to maximal fall in forced expiratory volume in one second (FEV1) following exercise (r=0.302, P<0.01) and the index of airway hyperresponsiveness (AHR) to 4.5% saline (r=-0.232, P<0.05), but not methacholine (r=-0.125, P>0.05). CONCLUSIONS: Positive skin test reactions to HDMs and EIB occurred in winter, spring/fall, and summer in decreasing order of frequency. Seasonal variation in the prevalence of EIB may be related to seasonal variation in sensitization to HDMs, accompanied by differences in indirect, but not direct, AHR.
Allergens ; Asthma ; Asthma, Exercise-Induced ; Bronchoconstriction ; Forced Expiratory Volume ; Humans ; Male ; Medical Records ; Methacholine Chloride ; Pollen ; Prevalence ; Pyroglyphidae ; Seasons ; Skin ; Skin Tests ; Young Adult

PURPOSE: Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy. METHODS: This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma). RESULTS: Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452). CONCLUSIONS: These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.
Adrenal Cortex Hormones ; Albuterol ; Anti-Bacterial Agents ; Asthma ; Humans ; Inhalation ; Nebulizers and Vaporizers ; Odds Ratio ; Prescriptions ; Primary Health Care ; Respiratory System ; Retrospective Studies

The rising incidence of allergic disorders in developed countries is unexplained. Exposure to traffic related air pollutants may be an important cause of wheezing and asthma in childhood. Experimental evidence from human studies suggests that diesel exhaust particles, constituents of fine particulate matter less than 2.5 microns (PM2.5), may act to enhance IgE mediated aeroallergen sensitization and Th2 directed cytokine responses. To date, epidemiologic investigations indicate that children living in close proximity to heavily travelled roads are more likely to be atopic and wheeze. The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort study was initiated to test the hypothesis that early high exposure to traffic related air pollutants is associated with early aeroallergen sensitization and allergic respiratory phenotypes. Using an exposure cohort design, more than 700 infants born to atopic parents were recruited at age 1 living either less than 400 meters (high traffic pollutant exposure) or greater than 1,500 meters (low exposure) from a major road. Children were medically evaluated and underwent skin prick testing with aeroallergen at screening, and re-evaluated sequentially at ages 1, 2, 3, 4, and 7. In this study, both proximity and land use regression (LUR) models of traffic air pollutant exposure have been assessed. Proximity to stop and go traffic with large concentrations of bus and truck traffic predicted persistent wheezing during infancy. The LUR model estimated elemental carbon attributable to traffic (ECAT) as a proxy for diesel exhaust particulate exposure. High ECAT was significantly associated with wheezing at age 1 as well as persistent wheezing at age 3. High mold exposure predicted a well defined asthma phenotype at age 7.
Air Pollutants ; Air Pollution ; Asthma ; Carbon ; Child ; Cohort Studies ; Developed Countries ; Fungi ; Humans ; Hypersensitivity ; Immunoglobulin E ; Incidence ; Infant ; Mass Screening ; Motor Vehicles ; Parents ; Particulate Matter ; Parturition ; Phenotype ; Proxy ; Respiratory Sounds ; Skin ; Sneezing ; Vehicle Emissions

The nose and lung are both part of the respiratory tract. Often the diseases affecting the nose and/or the bronchi are treated separately. However, in recent years, numerous studies have highlighted the fact that the respiratory system is a single entity and the concept of "united airway disease" has become more and more important. The unity of the respiratory tract is confirmed both from a morphological and from a functional point of view. Nevertheless, this concept is also confirmed for the respiratory immune system, innervation and vascularization interesting all along the tract, from the nose to the bronchioles. When treating rhinitis, it is often necessary to assess the presence of asthma. Patients with sinusitis should be evaluated for a possible concomitant asthma. Conversely, patients with asthma should always be evaluated for possible nasal disease. The medications that treat nasal diseases appear to be useful in improving control of asthma and in reducing bronchial hyperresponsiveness as well. Physicians should always keep these notions in mind, and evaluate and treat respiratory diseases taking into account the unity of the respiratory tract.
Asthma ; Bronchi ; Bronchioles ; Humans ; Immune System ; Lung ; Nose ; Nose Diseases ; Respiratory System ; Rhinitis ; Rhinitis, Allergic, Perennial ; Sinusitis

No abstract available.
Asthma ; Nebulizers and Vaporizers

PURPOSE: Because bronchodilator response (BDR) is variable among asthmatic patients, there are practical limitations in using BDR to assess asthma control. We investigated the relationships of BDR with asthma control status and fractional exhaled nitric oxide (FeNO) in children with atopic asthma. METHODS: One hundred ninety-one patients aged 8 to 16 years with atopic asthma were enrolled. Pulmonary function tests including BDR and FeNO were serially measured 10 times or more over 2 years when subjects were not receiving controller medications. During the last year of follow-up, the loss of asthma control was assessed in all participants. RESULTS: We identified 114 children (60%) with at least 1 positive BDR (> or =12%) over the 2-year observation period. Higher levels of BDRs and higher rates of positive BDRs were associated with lower lung function and lower methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second). The loss of asthma control occurred in 106 of individuals (93%) who had positive BDRs, as compared to 52 of 77 (68%) with negative BDRs (P<0.001). There was no difference in FeNO levels between individuals with positive and negative BDRs. However, among children with negative BDRs, those developing the loss of asthma control had higher maximal FeNO levels and higher rates of FeNO>21 parts per billion than those who maintained asthma control (all P<0.001). CONCLUSION: Positive BDRs are linked to a higher probability of asthma control loss in children with atopic asthma. In addition, high FeNO is associated with asthma control loss in asthmatic children with negative BDRs.
Asthma* ; Child* ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Lung ; Methacholine Chloride ; Nitric Oxide* ; Respiratory Function Tests

PURPOSE: The relationship between vitamin D status and pulmonary function has been investigated in several studies. But previous study results are controversial. We want to know the relationship between vitamin D status and pulmonary function in Korean adults in small regional area. METHODS: The medical records of 3,253 subjects were reviewed retrospectively, those visited for routine health examination in Samsung Changwon Hospital between January and December 2013. All of them were workers in one company and lived in one island ('Geojedo'). RESULTS: Vitamin D deficiency group (serum 25-hydroxyvitamin D [25(OH)D]<20 ng/mL) showed lowed % forced vital capacity in one second (%FEV1; P<0.01), forced vital capacity (FVC; P<0.01) and higher FEV1/FVC (P<0.01). Serum 25(OH)D was positively correlated with %FEV1 (R=0.035, P<0.05), %FVC (R=0.081, P<0.01), FVC (R=0.125, P<0.01) and negatively with FEV1/FVC (R=-0.083, P<0.01). After adjustment for smoking history, we found serum 25(OH)D level was positively correlated with %FVC (R=0.058, P<0.01), FVC (R=0.093, P<0.01) and negatively with FEV1/FVC (R=-0.055, P<0.01). After adjustment for smoking and asthma history, we found serum 25(OH)D level was positive correlated with %FVC (R=0.103, P<0.01) and negatively with FEV1/FVC (R=-0.119, P<0.01). CONCLUSION: Serum 25(OH)D level was associated with pulmonary function.
Adult* ; Asthma ; Forced Expiratory Volume ; Gyeongsangnam-do ; Humans ; Lung* ; Medical Records ; Respiratory Function Tests ; Retrospective Studies ; Smoke ; Smoking ; Vital Capacity ; Vitamin D ; Vitamin D Deficiency