Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.

OBJECTIVES: The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. METHODS: Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. RESULTS: Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. CONCLUSIONS: Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

HLA and asthma phenotypes/endotypes: a review.

Asthma is a complex chronic inflammatory disease of the airways caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWAS) represent the most powerful approach for asthma, that have identified several genes (e.g., IL18R1, IL33, SMAD3, ORMDL3, HLA-DQ and IL2RB loci). HLA super-locus is a genomic region in the chromosomal position 6p21. Since no gene can be considered as an asthma gene, able to reflect the complex etiology and the heterogeneity of the disease the terms 'phenotype' and more recently 'endotype' have been used. This review, according to literature availability, focuses on the relationship between human leukocyte antigens (HLA) region specifically the HLA class II genes and different asthma phenotypes/endotypes, such as allergic asthma/Th2 associated, occupational and aspirin-sensitive asthma. The most common HLA haplotypes in the different asthma phenotypes are HLA-DRB1in allergic asthma, HLA-DQB1in occupational asthma and HLA-DPB1 in aspirin-sensitive asthma. However, it is difficult to study the role of class II genes in vivo because of the heterogeneity of human population, the complexity of MHC, and the strong linkage disequilibrium among different class II genes. Despite the variation and the inconsistency of the HLA haplotypes and alleles in different types of asthma, the association between HLA class II genes and asthma has been demonstrated in the majority of studies.

Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells appear to be involved in the development of interstitial lung diseases (ILD). The purpose of this study was to investigate the involvement of NK and natural killer T (NKT)-like cells in two recognized cytotoxic ILD with systemic character, hypersensitivity pneumonitis (HP) and cryptogenic organizing pneumonia (COP), compared with idiopathic pulmonary fibrosis (IPF) and controls. METHODS: Bronchoalveolar lavage fluid (BALF) and peripheral blood (PBL) cells and lymphocyte subsets of 83 patients (26 with COP, 19 with HP and 38 with IPF) and 10 controls were prospectively studied by flow cytometry. RESULTS: The percentage of NK and NKT-like cells was lower in BALF than in PBL in all patient groups and controls. Patients with COP presented with statistically significantly higher NK and NKT-like cell counts in BALF compared with controls (P = 0.044 and P = 0.05 respectively) and IPF (P = 0.049 and P = 0.045 respectively). BALF NKT-like cell count correlated with PBL NKT-like cell count only in COP (r = 0.627, P = 0.002). In addition, a significant positive correlation between BALF NKT-like cell and PBL cytotoxic T CD8+ cell count was observed in COP (r = 0.562, P = 0.006) but not in HP, IPF or controls. CONCLUSIONS: Our study provides for the first time evidence for the implication of NKT-like cells in the pathogenesis of COP, as part of both localized and systemic cytotoxicity.

Asthma control test is correlated to FEV1 and nitric oxide in Greek asthmatic patients: influence of treatment.

BACKGROUND: Asthma is a common chronic disease affecting patients' health status and quality of life. Although recent guidelines focus on asthma control, asthma remains poorly controlled in many patients even under specialist care. Asthma Control Test™ (ACT) is a short, simple, patient-based tool that provides consistent assessment of asthma. OBJECTIVE: The aim of this study was to estimate the relationship of ACT with objective measures of lung function and inflammation such as forced expiratory volume in 1st second (FEV(1)) and exhaled nitric oxide (FeNO) in outpatients admitted for initial diagnosis of asthma and at follow-up. METHODS: One hundred and sixty (104 women and 56 men, mean age 39.7 ± 16.6 years) asthmatic patients with newly diagnosed asthma were included in the study. Patients completed the ACT questionnaire and underwent a detailed clinical examination, FeNO measurement, and prebronchodilator spirometry before (visit 1) and 4-12 weeks after initiation of treatment (visit 2). RESULTS: At visit 1, the mean ACT score was 21.27 ± 3.74. According to ACT score, 37 patients (23.1%) were completely controlled, 85 patients (53.1%) were partly controlled, and 38 patients (23.8%) were uncontrolled. Patients with uncontrolled asthma had statistically higher FeNO values than patients with partly controlled (p = .038) and completely controlled asthma (p = .016). ACT score was found to have a positive correlation with prebronchodilator %FEV(1) (r = 0.177, p = .025) and negative correlation with FeNO ( r = -0.211, p = .007). At visit 2, the mean ACT score was 23.00 ± 2.19. The change in ACT score between the two visits was significantly correlated to changes in FEV(1) (r = 0.538, p < .001) and in FeNO (r = -0.466, p < .001). Patients treated with inhaled corticosteroids (ICSs) showed significant improvement in FEV(1) and in ACT score and a decrease in FeNO compared with patients without ICS treatment. CONCLUSION: Although FEV(1) remains the main objective parameter for evaluating asthma, ACT score was found to reflect lung function and inflammation in a Greek asthmatic population.