An Analysis of Factors that Exacerbate Asthma, Based on a Japanese Questionnaire

ABSTRACTBackgroundIt is known that a wide variety of factors exacerbate asthma; however, few studies have investigated the factors that exacerbate asthma from a patient's perspective. The aim of this study was to analyze the factors that exacerbate asthma, based on a questionnaire completed by asthma patients in Niigata Prefecture.MethodsBased on questionnaires given to 3085 patients who visited the medical institutes in the Niigata Prefecture monthly from September through October 2006, groups stratified by sex, age, disease type and disease severity, were analyzed for factors contributing to asthma exacerbation, as described in the guideline of the Japanese Society of Allergology.ResultsThe leading exacerbating factor chosen by patients was a change in the weather, followed by smoking, allergen exposure, fatigue, stimulants, and air pollutants. Respiratory infection, widely recognized as a critical factor of severe exacerbation, was ranked seventh. Allergen exposure and air pollutants were prominent in younger individuals, whereas respiratory infection tended to be more common in elderly subjects. Allergen exposure, air pollutants, and exercise were significantly more common in atopic-type patients, in contrast with respiratory infection in non-atopic-type patients. According to multiple regression analysis, poor asthma control during the last one year was associated with changes in the weather, whereas the non-atopic disease type was related to exacerbation by respiratory infection. Current smoking was associated with both factors.ConclusionsMany factors exacerbate asthma, depending on the individual case and his/her background. These data suggest that changes in the weather may be more important factor for patients in asthma exacerbation

CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression

CD4+ T Responses Other Than Th1 Type Are Preferentially Induced by Latency-Associated Antigens in the State of Latent Mycobacterium tuberculosis Infection

Mycobacterium tuberculosis (M. tuberculosis) produces a diverse range of antigenic proteins in its dormant phase. The cytokine profiles of CD4+ T cell responses, especially subsets other than Th1 type (non-Th1 type), against these latency-associated M. tuberculosis antigens such as α-crystallin (Acr), heparin-binding hemagglutinin (HBHA), and mycobacterial DNA-binding protein 1 (MDP-1) remain elusive in relation to the clinical stage of M. tuberculosis infection. In the present study, peripheral blood mononuclear cells (PBMCs) collected from different stages of M. tuberculosis-infected cases and control PBMCs were stimulated with these antigens and ESAT-6/CFP-10. Cytokine profiles of CD4+ T cells were evaluated by intracellular cytokine staining using multicolor flow cytometry. Our results demonstrate that Th1 cytokine responses were predominant after TB onset independent of the type of antigen stimulation. On the contrary, non-Th1 cytokine responses were preferentially induced by latency-associated M. tuberculosis antigens, specifically IL-10 response against Acr in latent M. tuberculosis infection. From these results, we surmise a shift in the CD4+ T cell response from mixed non-Th1 to Th1 dominant type during TB progression

Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB.

Background Disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signalling causes pulmonary alveolar proteinosis (PAP). Rarely, genetic defects in neonatal or infant-onset PAP have been identified in CSF2RA. However, no report has clearly identified any function-associated genetic defect in CSF2RB. Methods and results The patient was diagnosed with PAP at the age of 36 and developed respiratory failure. She was negative for GM-CSF autoantibody and had no underlying disease. Signalling and genetic defects in GM-CSF receptor were screened. GM-CSF-stimulated STAT5 phosphorylation was not observed and GM-CSF-Rβc expression was defective in the patient\u27s blood cells. Genetic screening revealed a homozygous, single-base deletion at nt 631 in exon 6 of CSF2RB on chromosome 22, which caused reductions in GM-CSF dependent signalling and function. Both parents, who were second cousins, showed no pulmonary symptoms, and had normal GM-CSF-signalling, but had a CSF2RB allele with the identical deletion, indicating that the mutant allele may give rise to PAP in an autosomal recessive manner. Conclusions This is the first report identifying a genetic defect in CSF2RB that causes deficiency of GM-CSF-Rβc expression and impaired signalling downstream. These results suggested that GM-CSF signalling was compensated by other signalling pathways, leading to adult-onset PAP

HLA-Associated Immune Pressure on Gag Protein in CRF01_AE-Infected Individuals and Its Association with Plasma Viral Load

BACKGROUND: The human leukocyte antigen (HLA)-restricted cytotoxic T-lymphocyte (CTL) immune response is one of the major factors determining the genetic diversity of human immunodeficiency virus (HIV). There are few population-based analyses of the amino acid variations associated with the host HLA type and their clinical relevance for the Asian population. Here, we identified HLA-associated polymorphisms in the HIV-1 CRF01_AE Gag protein in infected married couples, and examined the consequences of these HLA-selected mutations after transmission to HLA-unmatched recipients. METHODOLOGY/PRINCIPAL FINDINGS: One hundred sixteen HIV-1-infected couples were recruited at a government hospital in northern Thailand. The 1.7-kb gag gene was amplified and directly sequenced. We identified 56 associations between amino acid variations in Gag and HLA alleles. Of those amino acid variations, 35 (62.5%) were located within or adjacent to regions reported to be HIV-specific CTL epitopes restricted by the relevant HLA. Interestingly, a significant number of HLA-associated amino acid variations appear to be unique to the CRF01_AE-infected Thai population. Variations in the capsid protein (p24) had the strongest associations with the viral load and CD4 cell count. The mutation and reversion rates after transmission to a host with a different HLA environment varied considerably. The p24 T242N variant escape from B57/58 CTL had a significant impact on the HIV-1 viral load of CRF01_AE-infected patients. CONCLUSIONS/SIGNIFICANCE: HLA-associated amino acid mutations and the CTL selection pressures on the p24 antigen appear to have the most significant impact on HIV replication in a CRF01_AE-infected Asian population. HLA-associated mutations with a low reversion rate accumulated as a footprint in this Thai population. The novel HLA-associated mutations identified in this study encourage us to acquire more extensive information about the viral dynamics of HLA-associated amino acid polymorphisms in a given population as effective CTL vaccine targets

Unique CRF01_AE Gag CTL Epitopes Associated with Lower HIV-Viral Load and Delayed Disease Progression in a Cohort of HIV-Infected Thais

Cytotoxic T Lymphocytes (CTLs) play a central role in controlling HIV-replication. Although numerous CTL epitopes have been described, most are in subtype B or C infection. Little is known about CTL responses in CRF01_AE infection. Gag CTL responses were investigated in a cohort of 137 treatment-naïve HIV-1 infected Thai patients with high CD4+ T cell counts, using gIFN Enzyme-Linked Immunospot (ELISpot) assays with 15-mer overlapping peptides (OLPs) derived from locally dominant CRF01_AE Gag sequences. 44 OLPs were recognized in 112 (81.8%) individuals. Both the breadth and magnitude of the CTL response, particularly against the p24 region, positively correlated with CD4+ T cell count and inversely correlated with HIV viral load. The breadth of OLP response was also associated with slower progression to antiretroviral therapy initiation. Statistical analysis and single peptide ELISpot assay identified at least 17 significant associations between reactive OLP and HLA in 12 OLP regions; 6 OLP-HLA associations (35.3%) were not compatible with previously reported CTL epitopes, suggesting that these contained new CTL Gag epitopes. A substantial proportion of CTL epitopes in CRF01_AE infection differ from subtype B or C. However, the pattern of protective CTL responses is similar; Gag CTL responses, particularly against p24, control viral replication and slow clinical progression

Comparison of Cytoreductive Surgery and Resection of Isolated Peritoneal Metastases in Patients with Peritoneal Metastases from Colorectal Cancer: A Retrospective Study

Objectives: This study aimed to compare the short and long-term outcomes of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy and resection of isolated peritoneal metastases in patients with peritoneal metastases from colorectal cancer in Japan. Methods: We included patients who had undergone surgery for peritoneal metastases from colorectal cancer between 2013 and 2019. Data were retrieved from a prospectively maintained multi-institutional database and retrospective chart review. Patients were classified into cytoreductive surgery and resection of isolated peritoneal metastases groups based on the surgery they had undergone. Results: A total of 413 patients were eligible for analysis (257 and 156 patients in the cytoreductive surgery and resection of isolated peritoneal metastases groups, respectively). There was no significant difference in overall survival (hazard ratio and 95% confidence intervals, 1.27 [0.81, 2.00]). Six cases (2.3%) of postoperative mortality were observed in the cytoreductive surgery group, whereas none were observed in the resection of the isolated peritoneal metastases group. Cases of postoperative complications were significantly higher in the cytoreductive surgery group (risk ratio 2.02 [1.18, 2.48]) than those in the resection of isolated peritoneal metastases group. Among patients with a high peritoneal cancer index (6 points or higher), the complete resection rate was 115/157 (73%) and 15/44 (34%) in the cytoreductive surgery and the resection of isolated peritoneal metastases groups, respectively. Conclusions: Cytoreductive surgery was not superior in providing long-term survival benefits for colorectal cancer peritoneal metastases; however, cytoreductive surgery provided a higher complete resection rate even in patients with a high peritoneal cancer index (6 points or higher)