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Association between asthma control test, pulmonary function tests and non-specific bronchial hyperresponsiveness in assessing the level of asthma control.

INTRODUCTION: Global Initiative for Asthma (GINA) reports emphasize the use of validated and simple tools in order to assess the level of asthma control, as the Asthma Control Test (ACT). However, an ACT does not include assessment of airway inflammation, which is better reflected when measuring nonspecific bronchial hyperresponsiveness (BHR). The authors aimed to find out if the level of asthma control quantified by an ACT correlates with BHR and pulmonary function tests.

MATERIAL AND METHODS: 118 asthmatics participated in the study. All patients completed an ACT. The scores of the ACTs were compared with pulmonary function tests and BHR assessed with the methacholine challenge test and expressed as a provocative concentration of methacholine, inducing a 20% decline in the FEV₁ (PC20 M in mg/ml).

RESULTS: Patients with controlled asthma amounted to 52 (44%) while those with uncontrolled asthma amounted to 66 (56%). In patients with controlled asthma (ACT score ≥ 20) the mean geometric value of PC₂₀M was 2.72 mg/ml (range from 0.25 to > 8.0), whereas 0.94 mg/ml (range from 0.28 to 8.0) (p = 0.02) was observed in patients with uncontrolled asthma (ACT score < 20). Almost 64% (21/33) uncontrolled asthmatics achieved normal lung function (FEV1 > 80% pred. value) while 19% (5/26) patients with controlled asthma presented an FEV1 < 80% predicted value. Asthma duration in years in controlled asthmatics was significantly shorter than in uncontrolled patients (6.2 ± 8.9 vs. 12.0 ± 11.4, p = 0.005)

CONCLUSION: In determining the most accurate level of asthma control it is reasonable to use an ACT in conjunction with BHR, which provides more accurate assessment of bronchial inflammation than spirometry alone.

Therapeutic Effects of Vitamin D in Asthma and Allergy.

In recent years, low vitamin D status has been proposed as a putative risk factor for allergic diseases.

A growing body of literature reports low vitamin D levels in atopic patients and supports an association between vitamin D deficiency and risk of adverse asthma and allergies outcomes. Therefore, it has been speculated that vitamin D supplementation may either prevent or reduce the risk of allergic diseases. Birth cohort studies addressing the role of vitamin D intake during pregnancy have shown conflicting results regarding allergy outcomes in offspring.

Currently, only a few studies have tried to supplement vitamin D in asthmatic patients, often as an add-on therapy to standard asthma controller medications, and results are not all consistent. There is emerging data to show that vitamin D can enhance the anti-inflammatory effects of glucocorticoids and potentially be used as adjuvant therapy in steroid-resistant asthma. Recent in vivo data suggest that vitamin D supplementation may also reduce the severity of atopic dermatitis.

This review examines the existing relevant literature focusing on vitamin D supplementation in the treatment of allergic diseases.

Vitamin D metabolism genes in asthma and atopy.

Asthma and allergy are complex diseases influenced by poorly understood environmental and genetic factors. The innate and adaptive immune systems play an important role in the pathogenesis of these diseases. Many genes involved in inflammation and immunoregulation pathways have been related to asthma and allergy susceptibility.

Among the diverse extra-skeletal actions of vitamin D, growing evidence indicates that vitamin D is an important modulator of the immune system response and may influence the development of asthma and allergy susceptibility through different mechanisms. The vitamin D pathway is under the control of a set of polymorphic genes that code for key enzymes which regulate the synthesis and metabolism of vitamin D (i.e. CYP27A1, GC, CYP27B1 and CYP24A1) and of genes that encode for downstream mediators of vitamin D signalling (i.e. VDR, RXR, PPAR, NCOA and SMAD). This metabolism gene pathway is of fundamental importance in regulating vitamin D availability and biological response. Unravelling the role of vitamin D metabolism genes on asthma and atopy susceptibility may help to understand the impact of vitamin D on the development of these disorders.

This review article aims:

  1. to describe the genetics of the vitamin D pathway,
  2. to revise the potential mechanisms by which vitamin D pathway genes may affect the immune and respiratory systems predisposing to asthma and allergy disorders;
  3. and to summarize the influence of genetic variation on vitamin D pathway genes on the development of asthma and allergy.

Maternal vitamin D status and the development of asthma and allergy in early childhood.

Vitamin D has an indisputable immunodulatory role in both lung and immune system development, which is initiated during fetal life and is mainly accomplished in the first years of extrauterine life.

Several published studies have shown that low levels of vitamin D may increase the risk of developing asthma and allergic diseases. Moreover, vitamin D deficiency epidemic reported over the last decades coincides with an increase in the prevalence of asthma and allergies in westernized societies. Since placental transfer of 25(OH)D is the major source of vitamin D in the developing fetus, important questions concerning the impact of maternal vitamin D status on the outcome of pregnancy have arisen.

The aim of this review is to present the current evidence regarding the determinants of vitamin D status in pregnancy as well as its role in the development of asthma and allergies in early childhood.

Association of serum vitamin D with asthma and atopy in childhood: review of epidemiological observational studies.

During the last decades, vitamin D deficiency has re-emerged worldwide affecting not only population's bone health, but also several other conditions including asthma and allergies. Increasing number of published epidemiological studies in the last seven years have examined the role of vitamin D deficiency in childhood with several outcomes including asthma diagnosis, asthma disease severity, allergic sensitization and atopy.

This review presents evidence on this association from a systematic search in the literature of all available observational studies and their limitations.

A total of 33 studies were identified: 3 prospective, 16 case-control and 14 cross-sectional studies. Overall, most of the case-control studies tend to report that asthmatics have lower vitamin D levels/status as compared to healthy children, although most of these studies are mainly descriptive in nature and tend to provide only crude, unadjusted comparisons. Studies that investigated the association of vitamin D with the prevalence, development and/or severity of asthma gave mixed findings, with the exception of studies that focused on vitamin D and severity of asthma which suggest a positive association of vitamin D levels with better asthma control, reduced use of asthma medication, fewer asthma exacerbations and lower utilisation of health care facilities for urgent treatment. Insufficient evidence also exists for the association of inadequate vitamin D status with higher risk of atopic sensitization. The lack of adequate number of prospective studies, the variable definitions for case ascertainment, the wide age range of the participants, and commonly the inadequate control for confounders make inferences difficult.

Future studies are needed with a prospective design and repeated measurements of vitamin D to provide critical information on the timing and dosage of future vitamin D supplementation interventions.

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