SERPINA1 gene polymorphisms in a population-based ALSPAC cohort.

BACKGROUND: There is an association between persistent preschool wheezing phenotypes and school-age asthma. These wheezing/asthma phenotypes likely represent clinical entities having specific genetic risk factors. The SERPINA1 gene encodes α 1 -antitrypsin (AAT), and mutations in the gene are important in the pathophysiology of pulmonary diseases. We hypothesized that there might be an association between SERPINA1 gene polymorphisms and the risk of developing wheezing/school age asthma. OBJECTIVE: To examine 10 single nucleotide polymorphisms (SNPs) of SERPINA1 (rs6647, rs11832, rs17580, rs709932, rs1243160, rs2854254, rs8004738, rs17751769, rs28929470, and rs28929474) and relate them to childhood wheezing phenotypes and doctor-diagnosed asthma in the population-based Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. METHODS: Wheeze data, reports of physician-diagnosed asthma and data on the SERPINA1 gene SNPs, were available for 7964 children. Binary logistic regression was used to assess the associations between allele prevalence and wheezing and asthma phenotypes. P values were adjusted to account for multiple hypotheses using the Benjamini-Hochberg false discovery rate. RESULTS: Only within a subgroup of children with asthma who had no prior diagnosis of preschool wheeze was there a trend for association between rs28929474 (Glu342Lys, Pi*Z causing AAT deficiency; P = .0058, adjusted P = .058). No SNP was associated with wheezing and asthma in those with preschool wheeze. CONCLUSION: Analyzed SNPs in SERPINA1 are not associated with wheezing/asthma phenotypes. Only rs28929474, the most common pathologic SNP (Pi*Z) in the SERPINA1 gene, might be associated with a risk of developing school-age asthma without exhibiting preschool wheeze.

Quality of life of the family of children with asthma is not related to asthma severity.

The quality of life for the family is an important outcome of childhood asthma. The aim of the study was to describe the quality of life in families who have a child with asthma. The Pediatric Quality of Life Inventory Family Impact Module was completed by the parents of 527 children with asthma. The median overall score was 75.0 (interquartile range 63.9, 87.5). The following factors were independently associated with lower quality of life: additional difficulties such as anxiety and financial hardship (3.81 [2.45, 5.93]), waking with asthma symptoms one or more nights a week (odds ratio 2.53 [1.34, 4.75]), regular use of symptoms reliever medication (2.47 [1.57, 3.87]), and female gender (1.97 [1.27, 3.05]). Lower socioeconomic status of the family and exposure to molds at home doubled the odds for lower quality of life. Physician's diagnosed asthma severity and control were associated with quality of life in univariate, but not multivariate analysis.Conclusion: Multiple factors, several of which are not related to asthma, contribute to the family burden of having a child with asthma. Clinicians should be mindful of the impact of asthma on the child and the family, and consider exploring factors not directly related to childhood asthma. What is Known: • Childhood asthma as a chronic disease impacts the quality of life of the patient, but there is also an impact on the immediate family. • There are relatively few studies exploring the quality of life of parents of a child with asthma; the results are heterogeneous and none has been carried out in an Eastern European country. What is New: • This is the first study to describe caregiver's quality of life in an Eastern European population in the context of childhood asthma. • The quality of life of the family of asthmatic child depends not only on factors related to asthma, but also non-asthma related factors such as poverty which play even more important role.

Antibiotic resistance of Streptococcus pneumoniae, isolated from nasopharynx of preschool children with acute respiratory tract infection in Lithuania.

BACKGROUND: Increasing pneumococcal resistance to commonly used antibiotics and multidrug resistance is a serious public health concern. Data on distribution of resistant Streptococcus pneumoniae (SPn) strains among children in Lithuania are limited. We evaluated the circulation of SPn serotypes and antimicrobial susceptibility among preschool children in Lithuania before the introduction of universal infant pneumococcal vaccination. METHODS: A prospective study was carried out from February 2012 to March 2013 in five cities of Lithuania. A total of 900 children under six years of age who presented to primary care centre or a hospital emergency department with acute respiratory tract infection were enrolled in the study. Nasopharyngeal swabs were obtained and cultured for SPn. Positive samples (n = 367) were serotyped and tested for antimicrobial susceptibility. Associations of pneumococcal non-susceptibility with study site, season, age, sex, attendance of day care centre and treatment with antimicrobials (between one and six months prior the study) were evaluated. RESULTS: About a half (56.7 %) of SPn strains were susceptible to all the antibiotics tested. Pneumococcal non-susceptibility to penicillin, erythromycin, clindamycin and trimethoprim-sulphamethoxazole was 15.8, 21.3, 16.9 and 27.3 %, respectively. None of the tested isolates was resistant to norfloxacin or vancomycin. We found a geographical variation of pneumococcal resistance within the cities of the country. Age, sex, the attendance of day care centre and treatment with antimicrobials prior the study was not significantly associated with a carriage of non-susceptible SPn strains. Among non-susceptible SPn serotypes 67.9 %-82.4 % were present in currently available pneumococcal conjugate vaccines. CONCLUSIONS: The rates of nasopharyngeal SPn susceptibility to penicillin and macrolides are still high among preschool children in Lithuania, however they are lower compared with previous studies. A strict policy with respect to antibiotic prescription together with widespread use of vaccination could potentially reduce the carriage rate of antibiotic-resistant pneumococci in our country.

The influence of Streptococcus pneumoniae nasopharyngeal colonization on the clinical outcome of the respiratory tract infections in preschool children.

BACKGROUND: Streptococcus pneumoniae (SPn) is an important pathogen causing a variety of clinical manifestations. The effects of SPn nasopharyngeal colonization on respiratory tract infections are poorly studied. We evaluated the association of SPn colonization with features of respiratory tract infections. METHODS: Children under the age of 6 years who visited a primary care physician because of respiratory tract infections were enrolled in the study. History was taken, children were clinically assessed by the physician, and nasopharyngeal swabs were obtained and cultured for SPn. Positive samples were serotyped. Associations of SPn colonization with clinical signs and symptoms, recovery duration, absence from day care centre, frequencies of specific diagnoses, and treatment with antimicrobials were evaluated. RESULTS: In total 900 children were enrolled. The prevalence of SPn colonization was 40.8 % (n = 367). There were minor differences between male and female subjects (199 of 492, 40.4 % vs 168 of 408, 41.2 %, p = 0.825). Children with and without siblings had similar colonization rates (145 of 334, 43.4 % vs 219 of 562, 39.0 %, p = 0.187). Clinical signs and symptoms were not associated with SPn colonization. Children colonized with SPn had longer recovery duration compared to non-colonized children (114 of 367, 31.1 % vs 98 of 533, 18.4 %, p < 0.001) and were longer absent from day care (270 of 608, 44.4 % vs 94 of 284, 33.1 %, p = 0.001). Pneumonia, sinusitis, and acute otitis media were more frequently diagnosed in children colonized with SPn. Children attending day care centres had significantly higher prevalence of SPn colonization (270 of 367, 44.4 % vs 338 of 533, 33.1 %, p = 0.001). Children with pneumonia, sinusitis and acute otitis media were more frequently treated with antimicrobials than children with other diagnoses. CONCLUSIONS: SPn nasopharyngeal colonization has a negative impact on the course of respiratory tract infection, likely because of SPn being the cause of the disease or a complicating factor. It is also associated with and may be responsible for higher frequencies of bronchitis, pneumonia, acute otitis media, sinusitis and the need of antimicrobial treatment.