Providers' perspectives on the performance of primary healthcare centres in India: The missing link.

BACKGROUND: Primary healthcare centres (PHCs) form the foundation of the Indian public health system, and thus their effective functioning is paramount in ensuring the population's health. The World Health Organisation (WHO) has set six aspects of performance assessment for general health systems, which are hardly applicable to the PHC setup in a low- and middle-income country. The Primary Health Care Performance Initiative (PHCPI) has prescribed a framework with five domains consisting of 36 indicators for primary healthcare performance assessment from a policy point of view. For the assessment to be realistic, it should include inputs from stakeholders involved in care delivery, so this study examines the perspectives of healthcare providers at PHCs in India. METHODOLOGY: The authors used qualitative research methodology in the form of responsive evaluations of healthcare provider's interviews to understand the indicators of PHC performance. RESULTS AND CONCLUSION: The study results showed that healthcare providers considered efficient teamwork, opportunities for enhancing provider skills and knowledge, job satisfaction, effective PHC administration, and good community relationship as PHC performance assessment. These domains of performance could be considered the 'missing link' in PHC assessment, since they are deemed important by providers and did not coincide with the WHO aspects and the PHCPI performance assessment framework.

Primary health Centres' performance assessment measures in developing countries: review of the empirical literature.

BACKGROUND: It is universally accepted that primary healthcare is essential for achieving public health and that assessment of its performance is critical for continuous improvement. The World Health Organization's (WHO's) framework for performance assessment is a comprehensive global standard, but difficult to apply in developing countries because of financial and data constraints. This study aims to review the empirical literature on measures for Primary Health Centre (PHC) performance assessment in developing countries, and compare them for comprehensiveness with the aspects described by the WHO Framework. METHODS: Research articles published in English scientific journals between January 1979 and October 2016 were reviewed systematically. The reporting quality of the article and the quality of the measures were assessed with instruments adapted for the purpose of this study. Data was categorized and described. RESULTS: Fifteen articles were included in the study out of 4359 articles reviewed. Nine articles used quantitative methods, one article used qualitative methods exclusively and five used mixed methods. Fourteen articles had a good description of the measurement properties. None of the articles presented validity tests of the measures but eleven articles presented measures that were well established. Mostly studies included components of personnel competencies (skilled/ non-skilled) and centre performance (patient satisfaction/cost /efficiency). CONCLUSIONS: In comparison to the WHO framework, the measures in the articles were limited in scope as they did not represent all service components of PHCs. Hence, PHC performance assessment should include system components along with relevant measures of personnel performance beyond knowledge of protocols. Existing measures for PHC performance assessment in developing countries need to be validated and concise measures for neglected aspects need to be developed.

The effect of financial incentives on top of behavioral support on quit rates in tobacco smoking employees: study protocol of a cluster-randomized trial.

BACKGROUND: Stimulating successful tobacco cessation among employees has multiple benefits. Employees who quit tobacco are healthier, more productive, less absent from work, and longer employable than employees who continue to use tobacco. Despite the evidence for these benefits of tobacco cessation, a successful method to stimulate employees to quit tobacco is lacking. The aim of this study is to evaluate whether adding a financial incentive to behavioral support (compared with no additional incentive) is effective and cost-effective in increasing abstinence rates in tobacco smoking employees participating in a smoking cessation group training. METHODS/DESIGN: In this cluster-randomized trial employees in the intervention and control group both participate in a smoking cessation group training consisting of seven weekly counseling sessions of ninety minutes each. In addition to the training, employees in the intervention group receive a voucher as an incentive for being abstinent from smoking at the end of the training (€50), after three months (€50), after six months (€50), and after one year (€200). The control group does not receive any incentive. The primary outcome is carbon monoxide validated 12-month continuous abstinence from smoking (Russel's standard). Additionally, an economic evaluation is performed from a societal and an employer perspective. DISCUSSION: The present paper describes the methods and design of this cluster-randomized trial in detail. We hypothesize that the financial incentive for abstinence in the form of vouchers increases abstinence rates over and above the group training. The results of this study can provide important recommendations for enhancement of employee tobacco cessation. TRIAL REGISTRATION: Dutch Trial Register: NTR5657 . First received 27-01-2016.

The Healthy Primary School of the Future: study protocol of a quasi-experimental study.

BACKGROUND: Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined. METHODS: In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019. DISCUSSION: A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific foundation, these integrated programmes have the potential to form a template for primary schools worldwide. The effects of this approach may extend further than the outcomes associated with well-being and academic achievement, potentially impacting legal and cultural aspects in our society. TRIAL REGISTRATION: The study protocol was registered in the database ClinicalTrials.gov on 14-06-2016 with the reference number NCT02800616 .

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking.This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any "hardcore" smoker who finds it difficult to quit with standard approaches.

Methodological considerations in service use assessment for children and youth with mental health conditions; issues for economic evaluation.

Economic evaluations are increasingly used in decision-making. Accurate measurement of service use is critical to economic evaluation. This qualitative study, based on expert interviews, aims to identify best approaches to service use measurement for child mental health conditions, and to identify problems in current methods. Results suggest considerable agreement on strengths (e.g., availability of accurate instruments to measure service use) and weaknesses, (e.g., lack of unit prices for services outside the health sector) or alternative approaches to service use measurement. Experts also identified some unresolved problems, for example the lack of uniform definitions for some mental health services.

State-wise dynamics of the double burden of malnutrition among 15-49 year-old women in India: how much does the scenario change considering Asian population-specific BMI cut-off values?

This article assesses the gravity of the "double burden of malnutrition" across 21 states of India, through a comparative analysis of traditional and Asian population-specific BMI categorizations for overweight and obesity. This study analyzes data on ever-married women (15-49 years) from the National Family Health Survey (NFHS-2, 1998-1999; NFHS-3, 2005-2006). Findings depict that Indian women tilt toward high BMI resulting in a co-existence of under- and overweight populations, which portray a regional pattern. With Asian population-specific cut-offs, 11 states can be classified as "double burden states"; however, following traditional categorization, only 4 states face such dual pressure.

The Patient's Perspective on the Functioning of the Primary Healthcare Centres in Bangalore, India: An Illustrated Guide.

India's healthcare system is, for a large part, organized around a vast network of Primary Healthcare Centres (PHCs) that form the pillar on which the public healthcare sector functions. The World Health Organization (WHO) has emphasized the important role that PHCs play in strengthening community health and the provision of healthcare. Although a few studies have assessed specific elements of services offered by PHCs, only a few have studied the patients' perspectives on the functioning and performance of PHCs in the Indian context. A qualitative research methodology was employed to explore the opinions of 188 patients attending one of three PHCs in Bengaluru (India), using in-depth interviews and thematic analysis. Results showed that patients assessed PHC based on the nine themes that broadly can be classified into components of the center, and that of the personnel. The patients valued the behavioural aspects of the personnel during service delivery and should be configured into the PHC performance.

[Pharmacogenetics in the treatment of tobacco addiction]. / Farmacogenetica bij de behandeling van tabaksverslaving.

BACKGROUND: Smokers vary in their genetic susceptibility to become addicted to smoking and probably also in their reaction to smoking cessation pharmacotherapies. AIM: To provide an overview of the developments on the pharmacogenetics of the treatment of tobacco addiction. METHOD: Review article describing the biological processes associated with tobacco addiction, and the influence of genetic variants on smoking behavior and the efficacy of smoking cessation therapies. RESULTS: Several (combinations of) genetic variants in smoking-related genes influence nicotine dependence. Moreover, several genetic variants in smoking- and treatment-related genes seem to influence the efficacy of smoking cessation therapies which are distinctive for the different forms of pharmacotherapy, especially when they have a different mechanism-of-action. CONCLUSION: Much progress has been made in unraveling the (pharmaco)genetics of tobacco addiction, but much still remains to be done before genetically tailored smoking cessation therapy can be implemented in clinical practice.

["Mummy, can I join a sports club?" a qualitative study on the impact of health-promoting schools on health behaviours in the home setting]. / 'Mam, dat is eigenlijk niet zo gezond'.

OBJECTIVE/DESIGN: Information regarding school-based health-promoting interventions' potential effects in the home environment is scarce. Gaining more insight into this is vital to optimise interventions' potential. The Healthy Primary School of the Future (HPSF) is a Dutch initiative aiming to improve children's health and well-being by providing daily physical activity sessions and healthy school lunches. This qualitative study examines if and how HPSF influenced children's and parents' physical activity and dietary behaviours at home. METHOD: In 2018-2019, 27 semi-structured interviews were conducted with parents from two HPSF schools. Interviews were recorded and transcribed, and data were coded and interpreted through thematic analysis. RESULTS: HPSF resulted in various behavioural changes at home, initiated by both children and parents. Parents reported improvements in healthy behaviours, as well as compensatory, unhealthy behaviours. Reasons for behavioural change included increased awareness, perceived support to adopt healthy behaviours, and children asking for the same healthy products at home. Barriers to change included no perceived necessity for change, lack of HPSF-related information provision, and time and financial constraints. CONCLUSION: Both child-to-adult intergenerational learning and parent-initiated changes play an important role in the transfer of health behaviours from school to home and are therefore key mechanisms to maximise school-based health-promoting interventions' impact.

House dust mite avoidance measures for perennial allergic rhinitis: an updated Cochrane systematic review.

BACKGROUND: To assess the benefits and harms of measures designed to reduce house dust mite (HDM) exposure in the management of house dust mite-sensitive allergic rhinitis. METHODS: Systematic review of randomized controlled trials was made, in which HDM control measures have been evaluated in comparison with placebo or other HDM avoidance measures, in patients with clinically proven allergic rhinitis. RESULTS: Nine trials involving 501 participants satisfied the inclusion criteria. These trials have investigated the effectiveness of bedroom environmental control programmes involving the use of HDM impermeable bedding covers (n = 4), acaricides (n = 2), high-efficiency particulate air filters (n = 2) and, using a factorial design, acaricide and HDM impermeable bedding covers in isolation and combination (n = 1). Seven of the nine trials reported that, when compared with control, the interventions studied resulted in significant reductions in HDM load. Of the interventions studied to date, acaricides appear to be the most promising, although the findings from these studies need to be interpreted with care because of their methodological limitations. House dust mite impermeable bedding as an isolated intervention is unlikely to offer benefit. CONCLUSIONS: Trials have tended to be small and of poor methodological quality, making it difficult to offer any definitive recommendations. Interventions that achieve substantial reductions in HDM load may offer some benefit in reducing rhinitis symptoms. Isolated use of HDM impermeable bedding is unlikely to prove effective.

Symptoms, but not a biomarker response to inhaled corticosteroids, predict asthma in preschool children with recurrent wheeze.

BACKGROUND: A reliable asthma diagnosis is challenging in preschool wheezing children. As inhaled corticosteroids (ICS) are more effective in asthmatics than in children with transient wheeze, an ICS response might be helpful in early asthma diagnosis. METHODS: 175 children (aged two-four years) with recurrent wheeze received 200 µg Beclomethasone extra-fine daily for eight weeks. Changes in Exhaled Breath Condensate (EBC) biomarkers (pH, interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, IFN-γ, sICAM, and CCL-11), Fractional exhaled Nitric Oxide (FeNO), airway resistance, and symptoms were assessed. At six years of age a child was diagnosed as transient wheezer or asthmatic. Adjusted logistic regression analysis was performed with multiple testing correction. RESULTS: 106 transient wheezers and 64 asthmatics were analysed at six years of age. Neither changes in EBC biomarkers, nor FeNO, airway resistance, or symptoms during ICS trial at preschool age were related to asthma diagnosis at six years of age. However, asthmatics had more airway symptoms before the start of the ICS trial than transient wheezers (P < 0.01). DISCUSSION: Although symptom score in preschool wheezing children at baseline was associated with asthma at six years of age, EBC biomarkers, airway resistance, or symptom response to ICS at preschool age could not predict asthma diagnosis at six years of age.

Battling the obesity epidemic with a school-based intervention: Long-term effects of a quasi-experimental study.

BACKGROUND: School-based health-promoting interventions are increasingly seen as an effective population strategy to improve health and prevent obesity. Evidence on the long-term effectiveness of school-based interventions is scarce. This study investigates the four-year effectiveness of the school-based Healthy Primary School of the Future (HPSF) intervention on children's body mass index z-score (BMIz), and on the secondary outcomes waist circumference (WC), dietary and physical activity (PA) behaviours. METHODS AND FINDINGS: This study has a quasi-experimental design with four intervention schools, i.e., two full HPSFs (focus: diet and PA), two partial HPSFs (focus: PA), and four control schools. Primary school children (aged 4-12 years) attending the eight participating schools were invited to enrol in the study between 2015 and 2019. Annual measurements consisted of children's anthropometry (weight, height and waist circumference), dietary behaviours (child- and parent-reported questionnaires) and PA levels (accelerometers). Between 2015 and 2019, 2236 children enrolled. The average exposure to the school condition was 2·66 (SD 1·33) years, and 900 participants were exposed for the full four years (40·3%). After four years of intervention, both full (estimated intervention effect (B = -0·17 (95%CI -0·27 to -0·08) p = 0·000) and partial HPSF (B = -0·16 (95%CI-0·25 to -0·06) p = 0·001) resulted in significant changes in children's BMIz compared to control schools. Likewise, WC changed in favour of both full and partial HPSFs. In full HPSFs, almost all dietary behaviours changed significantly in the short term. In the long term, only consumption of water and dairy remained significant compared to control schools. In both partial and full HPSFs, changes in PA behaviours were mostly absent. INTERPRETATION: This school-based health-promoting intervention is effective in bringing unfavourable changes in body composition to a halt in both the short and long term. It provides policy makers with robust evidence to sustainably implement these interventions in school-based routine.

Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy.

Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene-environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes (TLR 1-6, 9 and 10, CD14, MD2, lipopolysaccharide-binding protein (LBP) and Dectin-1), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study). The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1-2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two- and three-factor gene-gene and gene-environment interactions were found (e.g. between sibship size, day-care and LBP SNP rs2232596). Larger sibship size is associated with increased total IgE levels. Furthermore, complex two- and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.

Can exhaled inflammatory markers predict a steroid response in wheezing preschool children?

BACKGROUND: The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. OBJECTIVE: We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. METHODS: An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 µg; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0-4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-γ, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. RESULTS: Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2-1.7) to 1.3 (1.1-1.5) kPa s/L, symptom score: 26 (23-28) to 28 (24-29), P < 0.01, respectively]. Only IL-10 and atopy had limited predictive value regarding a change in symptoms [ß (SE) =-0.13 (0.07), P = 0.08, ß (SE) = 2.05 (1.17), P = 0.08, respectively]. CONCLUSIONS AND CLINICAL RELEVANCE: We did not find convincing evidence that FeNO and EBC markers could predict an ICS response in preschool wheezers. Recommendations for future studies on this topic are given.

[Effects and costs of The Healthy Primary School of the Future]. / De effecten en kosten van de Gezonde Basisschool van de Toekomst.

OBJECTIVE: To study school lifestyle interventions for elementary school children (The Healthy Primary School of the Future). RESEARCH QUESTION: What are the effects of the introduction of increased physical activity with or without healthy nutrition on health behaviour and BMI of young children and what are the costs of this program? DESIGN: Prospective controlled non-randomized study with nearly 1700 children in Parkstad (South-East Netherlands). RESULTS: Preliminary results after two years show that the combination of increased physical activity and healthy nutrition result in a decreased BMIz-score (-0.036), increased physical activity alone in hardly any change (-0.10) while in the control group the BMIz-score increased (0.052). The net societal costs of the combination of physical activity and health nutrition costs were 1 euro per child per day. CONCLUSION: The study contributes to the increasing amount of evidence proving that lifestyle interventions are effective in reducing the obesity epidemic. Future studies will show whether a weight reduction in children will result in the prevention of chronic disease later on in life and what the cost reduction related to this result will be.

Comparison of two twice-daily doses of budesonide/formoterol maintenance and reliever therapy.

The aim of this study was to compare two budesonide/formoterol maintenance doses within the budesonide/formoterol maintenance and reliever therapy concept and to identify possible patient characteristics at baseline which would predict a better response to a higher than standard maintenance dose. A total of 8,424 patients with symptomatic asthma when using an inhaled corticosteroid (ICS) with or without a long-acting ß(2)-agonist were randomised to budesonide/formoterol 160/4.5 µg, one (1 × 2) or two (2 × 2) inhalations b.i.d. Patients used the same inhaler as needed for symptom relief. The primary outcome variable was time to first severe asthma exacerbation. In the total study population, the time to first severe asthma exacerbation was prolonged by 18% with 2 × 2 versus 1 × 2 (hazard ratio 0.82; p = 0.03). Lung function (peak expiratory flow) was the only statistically significant predictor of a better response to 2 × 2. The mean daily ICS doses were 737 and 463 µg in the 2 × 2 and 1 × 2 groups, respectively. In a real-life setting, budesonide/formoterol maintenance and reliever therapy at the 2 × 2 maintenance dose did prolong time to first severe exacerbation but at a higher medication load. Patients with low lung function benefited most from the higher maintenance dose.

Interaction of T-cell and antigen presenting cell co-stimulatory genes in childhood IgE.

It is likely that multiple genes contribute to immunoglobulin (Ig)E production. Co-stimulatory molecules are crucial for the cross-talk between antigen presenting cells and T-lymphocytes which drives the IgE response. We evaluated gene-gene interactions of haplotype tagging polymorphisms in a pathway of 24 co-stimulatory genes in relation to serum IgE levels. We assessed this at ages 1-2 yrs and 6-8 yrs in 3,062 Dutch children from a pooled data set of three birth cohorts: PIAMA (Prevention and Incidence Asthma and Mite Allergy), PREVASC (Prevention of Asthma in Children) and KOALA (Child, parents and health: lifestyle and genetic constitution). Single- and multi-locus associations with serum IgE levels (3rd versus 1st tertile) were evaluated by Chi-squared tests and the multifactor dimensionality reduction (MDR) method in the following co-stimulatory genes: VTCN1, TNFRSF4, TNFRSF18, TNFRSF14, TNFSF18, TNFSF4, CD28, CTLA4, ICOS, PDCD1, BTLA, CD80, CD86, HLA-G, CD274, PDCD1LG2, CD276, LILRA4, LILRB1, LILRB2, LILRB4, CD40, ICOSLG, and CD40LG. We found multiple statistically significant single-locus ((S)) and multi-locus ((M)) associations for the genes VTCN1(SM), TNFSF18(SM), TNFSF4(S), CD28(S), CTLA4(M), ICOS(S), BTLA(M), CD80(M), CD86(SM), CD274(SM), PDCD1LG2(M), LILRA4(SM), LILRB4(M), and CD40(SM) with serum IgE. Two-locus interactions of CD86 with VTCN1 and CD274 with LILRA4 were confirmed by logistic regression. In conclusion, serum IgE levels are regulated by multiple gene-gene interaction effects in the co-stimulatory pathway. We suggest using research strategies that model multiple gene-gene interactions in genetic studies.

TLR-related pathway analysis: novel gene-gene interactions in the development of asthma and atopy.

BACKGROUND: The toll-like receptor (TLR)-related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR-related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene-gene interactions in this pathway contribute to atopy and asthma development. METHODS: One hundred and sixty-nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide-binding/facilitating proteins, adaptors, interleukin-1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single- and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1-2 and 6-8 years] and asthma (6-8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi-squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis. RESULTS: Several genes in the TLR-related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene-gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene-gene interactions were identified with SNPs that did not have an effect on their own. CONCLUSION: Our unbiased approach provided suggestive evidence for interaction between several TLR-related pathway genes important in atopy and/or asthma development and pointed to novel genes.