Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells.

Virtually all living cells are encased in glycans. They perform key cellular functions such as immunomodulation and cell-cell recognition. Yet, how their composition and configuration affect their functions remains enigmatic. Here, we constructed isogenic capsule-switch mutants harboring 84 types of capsular polysaccharides (CPSs) in Streptococcus pneumoniae. This collection enables us to systematically measure the affinity of structurally related CPSs to primary human nasal and bronchial epithelial cells. Contrary to the paradigm, the surface charge does not appreciably affect epithelial cell binding. Factors that affect adhesion to respiratory cells include the number of rhamnose residues and the presence of human-like glycomotifs in CPS. Besides, pneumococcal colonization stimulated the production of interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractantprotein-1 (MCP-1) in nasal epithelial cells, which also appears to be dependent on the serotype. Together, our results reveal glycomotifs of surface polysaccharides that are likely to be important for colonization and survival in the human airway.

Investigating highly replicated asthma genes as candidate genes for allergic rhinitis.

BACKGROUND: Asthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion of individuals with asthma also present symptoms of AR, and patients with AR have a 5-6 fold increased risk of developing asthma. Thus, the relevance of asthma candidate genes as predisposing factors for AR is worth investigating. The present study was designed to investigate if SNPs in highly replicated asthma genes are associated with the occurrence of AR. METHODS: A total of 192 SNPs from 21 asthma candidate genes reported to be associated with asthma in 6 or more unrelated studies were genotyped in a Swedish population with 246 AR patients and 431 controls. Genotypes for 429 SNPs from the same set of genes were also extracted from a Singapore Chinese genome-wide dataset which consisted of 456 AR cases and 486 controls. All SNPs were subsequently analyzed for association with AR and their influence on allergic sensitization to common allergens. RESULTS: A limited number of potential associations were observed and the overall pattern of P-values corresponds well to the expectations in the absence of an effect. However, in the tests of allele effects in the Chinese population the number of significant P-values exceeds the expectations. The strongest signals were found for SNPs in NPSR1 and CTLA4. In these genes, a total of nine SNPs showed P-values <0.001 with corresponding Q-values <0.05. In the NPSR1 gene some P-values were lower than the Bonferroni correction level. Reanalysis after elimination of all patients with asthmatic symptoms excluded asthma as a confounding factor in our results. Weaker indications were found for IL13 and GSTP1 with respect to sensitization to birch pollen in the Swedish population. CONCLUSIONS: Genetic variation in the majority of the highly replicated asthma genes were not associated to AR in our populations which suggest that asthma and AR could have less in common than previously anticipated. However, NPSR1 and CTLA4 can be genetic links between AR and asthma and associations of polymorphisms in NPSR1 with AR have not been reported previously.

Nasal allergies in the Asian-Pacific population: Results from the Allergies in Asia-Pacific Survey.

BACKGROUND: The Allergies in Asia-Pacific Survey describes the symptoms, impact, and treatment of allergic rhinitis (AR) across Australia, China, Hong Kong, Malaysia, Singapore, Taiwan, Vietnam, and the Philippines. The Allergies in Asia-Pacific Survey was undertaken to further clarify the prevalence of physician-diagnosed nasal allergies (NAs), impact on quality-of-life (QOL), existing treatment paradigms and gaps, and NA medications currently used in treatment. METHODS: Thirty-three thousand three hundred seventy-eight households were screened for individuals, ≥4 years old, with a physician diagnosis of AR or NA and either symptoms or treatment in the past 12 months. Standardized questionnaires were used to make comparisons across regions. A total of 1043 adults and 192 children were included in the survey. RESULTS: Nine percent of participants were diagnosed with AR with two of three responding that their NAs were seasonal in nature. Nasal congestion was the most common and bothersome symptom of AR. Most participants reported that AR impacted their QOL with nearly one-half citing impairments in school/work performance/productivity. Sleep disturbances, secondary to AR, were also shown to be appreciable. Two-thirds of patients took medication for their AR. Less than one-quarter of survey respondents reported taking an intranasal corticosteroid and the satisfaction rate was similar to that of over-the-counter medications. The most common reasons cited for dissatisfaction were related to inadequate efficacy and bothersome side effects. CONCLUSION: AR appears to be extremely common across Asia-Pacific nations. Many individuals with AR suffer from symptoms that reduce QOL and treatment gaps exist with current therapies. Through identification of disease impact and highlighting treatment gaps, clinicians may better understand and treat AR, leading to improvements in overall patient satisfaction and QOL.

Nasal allergies in the Asian-Pacific population: results from the Allergies in Asia-Pacific Survey.

BACKGROUND: The Allergies in Asia-Pacific Survey describes the symptoms, impact, and treatment of allergic rhinitis (AR) across Australia, China, Hong Kong, Malaysia, Singapore, Taiwan, Vietnam, and the Philippines. The Allergies in Asia-Pacific Survey was undertaken to further clarify the prevalence of physician-diagnosed nasal allergies (NAs), impact on quality-of-life (QOL), existing treatment paradigms and gaps, and NA medications currently used in treatment. METHODS: Thirty-three thousand three hundred seventy-eight households were screened for individuals, ≥ 4 years old, with a physician diagnosis of AR or NA and either symptoms or treatment in the past 12 months. Standardized questionnaires were used to make comparisons across regions. A total of 1043 adults and 192 children were included in the survey. RESULTS: Nine percent of participants were diagnosed with AR with two of three responding that their NAs were seasonal in nature. Nasal congestion was the most common and bothersome symptom of AR. Most participants reported that AR impacted their QOL with nearly one-half citing impairments in school/work performance/productivity. Sleep disturbances, secondary to AR, were also shown to be appreciable. Two-thirds of patients took medication for their AR. Less than one-quarter of survey respondents reported taking an intranasal corticosteroid and the satisfaction rate was similar to that of over-the-counter medications. The most common reasons cited for dissatisfaction were related to inadequate efficacy and bothersome side effects. CONCLUSION: AR appears to be extremely common across Asia-Pacific nations. Many individuals with AR suffer from symptoms that reduce QOL and treatment gaps exist with current therapies. Through identification of disease impact and highlighting treatment gaps, clinicians may better understand and treat AR, leading to improvements in overall patient satisfaction and QOL.