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Biomedical subjects

S H Arshad

Publications and source records attributed to S H Arshad.

At least 19 recordsLinked to original sources
PubMed2006

The diagnosis of Brazil nut allergy using history, skin prick tests, serum-specific immunoglobulin E and food challenges.

BACKGROUND: Allergy to Brazil nut is a relatively common nut allergy and can be fatal. However, the evidence is lacking regarding the best approach to its diagnosis. OBJECTIVE: We sought to determine the relative merits of history, skin prick testing, measurement of serum-specific IgE and challenge in the diagnosis of Brazil nut allergy. METHODS: Fifty-six children and adults with a history of an allergic reaction to Brazil nut or evidence of sensitization were investigated by questionnaire (n=56), skin prick tests (SPTs) (n=53), measurement of serum-specific IgE to Brazil nut (n=54) and double-blind, placebo-controlled labial, and if necessary oral, challenges (n=19). RESULTS: Brazil nut allergy occurred in highly atopic individuals of any age with a strong family history of atopy. In 24 of 56 (43%), the history of an immediate reaction was sufficient to make a diagnosis with confidence and an oral challenge was considered unsafe. Of the 19 subjects undertaking the 'gold standard' test of a double-blind, placebo-controlled, food challenge, all six subjects with a SPT of at least 6 mm had a positive challenge and all three subjects with a SPT of 0 mm had a negative challenge. In the remaining 10 (53%) subjects, where SPT was between 1 and 5 mm and serum-specific IgE was less than 3.5 kU/L, an oral challenge was performed resulting in three positive and seven negative challenges. CONCLUSION: A combination of history, SPT and serum-specific IgE was adequate in achieving a diagnosis in the majority (77%) patients with suspected Brazil nut allergy. However, a doubtful history with SPT between 1 and 5 mm, or a serum-specific IgE less than 3.5 kU/L may require an oral challenge to help determine the risk of a Brazil nut allergic reaction.

Administration, Oral↗
PubMed2005

Efficacy and acceptability of a new topical skin lotion of sodium cromoglicate (Altoderm) in atopic dermatitis in children aged 2-12 years: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory allergic disease of children. The primary anti-inflammatory therapy is topical steroids. An effective treatment without the topical and systemic adverse effects of corticosteroids would be useful. Topical formulations of sodium cromoglicate have been researched in the past, but without consistent results. We report a trial of a new aqueous skin lotion of sodium cromoglicate (Altoderm) in children with AD. OBJECTIVES: To compare the efficacy, safety and acceptability of Altoderm lotion with a placebo control in the treatment of AD in children. METHODS: A double-blind, controlled study in which children aged 2-12 years with AD were randomized to 12 weeks of treatment with a lotion containing 4% sodium cromoglicate (Altoderm) or the lotion base. To be included subjects had to have a SCORAD score of > or = 25 and < or = 60 at both of two clinic visits 14 days apart. Subjects continued using existing treatment which included emollients and topical steroids. The primary outcome was the change in the SCORAD score. The two groups were compared for the change in the SCORAD score from the second baseline visit to the visit after 12 weeks of treatment using an analysis of variance. Secondary outcome measures included parents' assessment of symptoms, usage of topical steroids recorded on daily diary cards, and final opinions of treatment by parent and clinician. Parents were asked about adverse effects at each clinic visit and the responses recorded. RESULTS: Fifty-eight children were randomized to Altoderm and 56 to placebo and all were included in the intention-to-treat analysis. The mean +/- SD SCORAD scores at baseline were 41.0 +/- 9.0 (Altoderm) and 40.4 +/- 8.73 (placebo). These scores were reduced after 12 weeks by 13.2 (36%) with Altoderm and by 7.6 (20%) with placebo. The difference of 5.6 (95% confidence interval 1.0-10.3) is statistically significant (P = 0.018). Diary card symptoms improved with both treatments but the improvement was greater in the Altoderm-treated patients. Topical steroid usage was reduced in both groups and was larger in the Altoderm-treated patients. The differences were statistically significant for the mean of all symptoms, the overall skin condition and use of topical steroids. Those for itching and sleep loss were not. Treatment-related adverse events were reported in 11 subjects (Altoderm seven, placebo four). Most of these referred to irritation, redness and burning at the site of application. There were four reports of erythema and pruritus (Altoderm three, placebo one), and three reports of application site burning (Altoderm two, placebo one). None was reported as severe or very severe. CONCLUSIONS: These results show a clinically useful benefit of this sodium cromoglicate lotion in children with moderately severe AD.

Administration, Cutaneous↗
PubMed2005

Defining childhood atopic phenotypes to investigate the association of atopic sensitization with allergic disease.

AIMS: Although atopic sensitization is common in childhood, its relationship to clinical allergic disease remains incompletely understood. We therefore sought to explore this relationship by defining sensitization based atopic phenotypes. METHODS: Children were recruited at birth (n = 1456) and reviewed at 1, 2, 4 and 10 years. Skin prick testing (SPT) to common allergens was done at 4 (n = 980) and 10 years (n = 1036) with lung function (n = 981), bronchial challenge (n = 784) and serum IgE (n = 953) testing at 10. Atopic phenotypes were defined, by sensitization pattern, for children with SPT at both 4 and 10 years (n = 823). RESULTS: Of phenotyped children, 68.0% were never atopic, 4.3% early childhood atopic (only atopic at age 4), 16.5% chronic childhood atopics (at 4 and 10 years) and 11.2% delayed childhood atopics (only at 10). Never atopics showed small but identifiable prevalence of allergic diseases such as asthma, eczema and rhinitis. Amongst allergen-sensitized subjects, aeroallergen predominated over food sensitization throughout childhood. Chronic childhood atopics showed highest prevalence of lifetime plus persistent wheeze, eczema and rhinitis, increased prevalence of aeroallergen sensitization, some evidence of persistent food sensitization, significantly greater cord IgE than never atopics (P = 0.006), plus higher total IgE (P < 0.001) and bronchial hyper-responsiveness (P < 0.001) at 10 years than other phenotypes. CONCLUSION: A proportion of childhood eczema, rhinitis and asthma is nonatopic. The commonest childhood pattern of atopy is chronic sensitization, associated with early, persisting and clinically significant allergic disease. The currently accepted childhood 'Allergic March' may oversimplify the natural history of childhood atopy and allergic disease.

Allergens↗
PubMed2004

Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance.

BACKGROUND: Identifying the protective effect of a higher number of siblings is a significant finding in understanding the aetiology of allergic sensitization, asthma, eczema, and hayfever. Knowledge about causes behind the sibling effect may allow us to prevent atopic manifestations. OBJECTIVE: We tested the hypothesis that rising order of live offspring increases maternal immune tolerance (immune non-reactivity) against allergens. To this end, we investigated whether maternal IgE levels are associated with the number of live offspring. METHODS: In a cohort of 1456 newborns recruited between January 1989 and February 1990 on the Isle of Wight, UK, we determined maternal and cord serum IgE, and the order of live offspring. The data were analysed by means of linear and path analysis. RESULTS: Maternal and cord serum IgE were available in 820 mother-infant pairs with birth order information. We found that the number of live offspring significantly reduces maternal IgE. The decline was more prominent in mothers with atopy (n=268). The geometric means of IgE after the first, second, and third or higher delivery were 74.4, 66.6, and 43.0 kU/L, respectively. Findings of path analysis suggest a significant direct effect of birth order on maternal IgE, but no direct effect of birth order on cord serum IgE. CONCLUSION: The findings support that maternal immune tolerance against allergens may increase with increasing order of live offspring and thus pass on a lower risk of developing atopy in children of higher birth order.

Adult↗
PubMed2004

Effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a multinational randomized, controlled birth-cohort study -- 24 months results of the Study of Prevention of Allergy in Children in Europe.

BACKGROUND: Sensitization to house dust mite (HDM) is an important risk factor for the development of asthma and allergic disease in childhood. Higher levels of HDM allergen are linked to increased sensitization to HDM. OBJECTIVE: To study the effect of mite-impermeable mattress encasings and an educational package on the development of allergies in a newborn cohort. METHODS: Six hundred and ninety-six newborns at high risk of developing allergies were enrolled in three European countries (Germany, Austria, UK) in a prospective, randomized, controlled birth-cohort study. Children were randomly assigned to an intervention and control group. Intervention measures included the use of mite-impermeable mattress encasings for the child's bed and a simple educational package on allergen avoidance. The control group received basic information about allergies. Children were followed up at age 6, 12, 18 and 24 months. RESULTS: 80.9% of the children were followed up to the age of 24 months. No difference in the prevalence of sensitization to HDM (control vs. intervention group: 8.4% vs. 6.1%, P=0.33) or the development of symptoms (recurrent wheezing 10.3% vs. 10.7%, nocturnal cough 12.5% vs. 12.5%) or allergic diseases (asthma 3.5% vs. 5.1%, eczema 20.0% vs. 19.6%, rhinitis 28.9% vs. 25.8%) could be found between the control and intervention group. CONCLUSION: In this study, HDM avoidance did not show a protective effect on the development of sensitization to HDM or symptomatic allergy in children at age 24 months.

Allergens↗
PubMed2004

Characterisation of atopic and non-atopic wheeze in 10 year old children.

BACKGROUND: Wheezing occurs in both atopic and non-atopic children. The characteristics of atopic and non-atopic wheeze in children at 10 years of age were assessed and attempts made to identify whether different mechanisms underlie these states. METHODS: Children were seen at birth and at 1, 2, 4 and 10 years of age in a whole population birth cohort study (n = 1456; 1373 seen at 10 years). Information was collected prospectively on inherited and early life environmental risk factors for wheezing. Skin prick testing, spirometry, and methacholine bronchial challenge were conducted at 10 years. Wheezing at 10 years of age was considered atopic or non-atopic depending on the results of the skin prick test. Independent significant risk factors for atopic and non-atopic wheeze were determined by logistic regression. RESULTS: Atopic (10.9%) and non-atopic (9.7%) wheeze were equally common at 10 years of age. Greater bronchial hyperresponsiveness (p<0.001) and airways obstruction (p = 0.011) occurred in children with atopic wheeze than in those with non-atopic wheeze at 10 years. Children with atopic wheeze more often received treatment (p<0.001) or an asthma diagnosis for their disorder, although current morbidity at 10 years differed little for these states. Maternal asthma and recurrent chest infections at 2 years were independently significant factors for developing non-atopic wheeze. For atopic wheeze, sibling asthma, eczema at 1 year, rhinitis at 4 years, and male sex were independently significant. CONCLUSIONS: Non-atopic wheeze is as common as atopic wheeze in children aged 10 years, but treatment is more frequent in those with atopic wheeze. Different risk factor profiles appear relevant to the presence of atopic and non-atopic wheeze at 10 years of age.

Age of Onset↗
PubMed2004

Raised cord serum immunoglobulin E increases the risk of allergic sensitisation at ages 4 and 10 and asthma at age 10.

BACKGROUND: Evidence suggests that a raised level of cord serum IgE (CS-IgE) is a risk factor for allergic sensitisation. However, whether CS-IgE is a risk for asthma is controversial. A study was undertaken to investigate the association between CS-IgE levels and allergic sensitisation at 4 and 10 years of age and asthma at ages 1-2, 4 and 10. METHODS: CS-IgE was available for 1358 of 1456 children born between 1989 and 1990. The cohort was evaluated for allergic diseases at ages 1, 2, 4 and 10 years. Skin prick tests for six allergens were performed on 981 children at age 4 and 1036 at age 10. Asthma was defined based on a physician's diagnosis. Using logistic regression analysis, the risk of asthma and allergic sensitisation for raised levels of CS-IgE (> or =0.5 kU/l) was estimated. RESULTS: At ages 4 and 10 years 20.2% and 27.0% of children, respectively, had allergic sensitisation. The risk of allergic sensitisation was significantly associated with raised CS-IgE levels at ages 4 (OR 2.29) and 10 years (OR 1.73). The prevalence of asthma was 10.3% at age 1-2, 15.2% at age 4, and 12.8% at age 10. CS-IgE was not associated with asthma at age 1-2 and 4 but showed an increased relative risk at age 10 (OR 1.66, 95% CI 1.05 to 2.62). The association was stronger in children who did not develop allergic sensitisation at age 4 or 10 (OR 3.35, 95% CI 1.41 to 7.93). CONCLUSIONS: Raised cord serum IgE is a risk factor for allergic sensitisation at ages 4 and 10 years. This is the second study suggesting that CS-IgE is also a risk factor for asthma at age 10, probably related to the late onset of asthma. This association is not necessarily mediated by allergic sensitisation.

Asthma↗
PubMed2003

Characterization of wheezing phenotypes in the first 10 years of life.

BACKGROUND: Childhood wheezing illnesses are characterized into different phenotypes. However, severity of the disease associated with these phenotypes has not been extensively studied. OBJECTIVES: To determine characteristics of childhood wheezing phenotypes in the first decade of life using health outcomes plus measurements of atopy, lung function and bronchial hyper-responsiveness. METHODS: A whole population birth cohort (n = 1456) was prospectively studied to examine the natural history of childhood wheezing. Children were seen at 1, 2, 4 and 10 years for questionnaire completion and prospectively collected data used to define wheezing phenotypes. Assessment was made of adverse health outcomes plus spirometry, bronchial hyper-responsiveness, serum IgE measurement at 10 years and skin test sensitization at both 4 and 10 years for wheezing phenotypes. RESULTS: Phenotypic analysis identified that 37% early life wheezers (symptom onset by age 4 years) still wheezed at 10 years. These persistent wheezers showed significantly more physician-diagnosed asthma in early life (P < 0.005 at 2 years) than early transient wheezers (wheezing transiently with onset by age 4 years). Overall they experienced greater multiple hospital admissions (P = 0.024), specialist referral (P = 0.009) and use of inhaled (P < 0.001) and oral steroids (P < 0.001) than early transient wheezers. They also demonstrated enhanced bronchial hyper-responsiveness compared with early transient wheezers (P < 0.001). However, both groups of early life wheezers showed impairment of baseline lung function at 10 years in comparison with non-wheezers: FEV1 (P < 0.029) and FEV1/FVC ratio (P < 0.001) with persistent wheeze and PEF (P = 0.036) with early transient wheeze. Late-onset wheezers (onset from 5 years onwards) had similar BHR to persistent wheezers but maintained normal lung function at age 10 and had lower cumulative prevalence of adverse health outcomes than persistent wheezers. CONCLUSIONS: Persistent wheezing with early childhood onset is associated with substantial morbidity in the first decade of life in association with high levels of atopy, bronchial hyper-responsiveness and impaired lung function at 10 years of age. Late-onset wheezing in the first decade of life could harbour potential for similarly significant disease subsequently.

Age of Onset↗
PubMed2003

In vitro stability and immunoreactivity of the native and recombinant plant food 2S albumins Ber e 1 and SFA-8.

BACKGROUND: The ability of an intact protein to reach the circulatory system may be a prerequisite to allergenicity and many allergens, particularly those from plant foods, have been found to be consistently more resistant to digestion by pepsin than other proteins. OBJECTIVE: This study assessed the pepsinolytic stability of native 2S albumins from Brazil nut and sunflower seed and their recombinant versions produced in Pichia pastoris. The physicochemical stability of native and recombinant Brazil nut 2S albumins and recombinant sunflower seed 2S albumin was also assessed. The immunoreactivity of native Brazil nut 2S albumin and recombinant 2S albumins was compared using serum from patients allergic to Brazil nuts and animals immunized with native 2S albumins. METHODS: Digestibility was measured in simulated gastric fluid followed by SDS-PAGE. Circular dichroism spectra were used to analyse unfolding, as proteins were denatured by temperature, pH and guanidinium chloride. Immunoreactivity was assessed by immunoblot, RAST and ELISA. RESULTS: Brazil nut 2S albumin was significantly more resistant to proteolytic digestion than other Brazil nut proteins. It was also resistant to thermally and chemically induced denaturation. Equally high resistance to proteolytic digestion was observed with sunflower seed 2S albumin. The recombinant albumins mirrored their native counterparts in stability and immunoreactivity. CONCLUSION: The important food allergen Brazil nut 2S albumin is as stable to digestion as is sunflower seed 2S albumin, whose allergenicity has yet to be determined. The 2S albumins and their recombinant counterparts could not be easily denatured by physicochemical treatments. The results suggest that 2S albumin is the only Brazil nut protein to reach the gut immune system intact. The production of properly folded recombinant proteins will facilitate mechanistic studies as well as diagnostic testing and antigen-based therapies.

2S Albumins, Plant↗
PubMed2003

Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study.

BACKGROUND: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. METHOD: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). RESULTS: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). CONCLUSION: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.

Allergens↗
PubMed2003

Predicting persistent disease among children who wheeze during early life.

This study sought to determine factors influencing the persistence of early life wheezing up to the age of 10 yrs and to create a score identifying those with the highest risk of persistent disease. Children were seen at birth, 1, 2, 4 and 10 yrs in a whole population birth cohort study (n=1,456). Information was collected prospectively on wheeze prevalence and subjects were classified into wheezing phenotypes. Early life genetic and environmental risk factors were recorded and skin-prick testing (SPT) was performed at 4 yrs. Independently significant factors for persisting wheeze were identified at logistic regression and used to create a score for persistence. Wheezing persistence from the first 4 yrs to the age of 10 yrs occurred in 37% of early life wheezers. Independent significance for persistence was associated with asthmatic family history, atopic SPT at 4 yrs and recurrent chest infections at 2 yrs, whilst recurrent nasal symptoms at 1 yr conferred reduced risk. A cumulative risk score using these factors identified wheezing persistence in 83% scoring 4 and transience in 80% scoring 0. Thus, a combination of genetic predisposition, early life atopy and recurrent chest infections favours the persistence of early life wheezing. Risk scores using such knowledge could provide prognostic guidance on the outcome of early wheeze.

Asthma↗
PubMed2002

Prevention of sensitization to house dust mite by allergen avoidance in school age children: a randomized controlled study.

BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic rhinitis, and prevention of this sensitization might reduce the rising prevalence of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance measures on the development of sensitization to dust mites in children. METHODS: As part of a multicentre study (Study of Prevention of Allergy in Children of Europe), 242 children, aged 5-7 years, in three European countries (United Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127) and control group (n = 115). At randomization these children were required to have a family history of atopy and positive skin test to an aeroallergen but not to house dust mite. Children in the prophylactic group were provided with dust mite impermeable mattress covers and advice on environmental measures to reduce exposure to dust-mite allergen. Control group children were given non-specific advice. After 12 months a standardized questionnaire was completed and skin prick tests were performed. RESULTS: Ten children in the prophylactic group and 19 in the control group were lost to follow-up. Three of 117 (2.56%) children in the prophylactic group and nine of 96 (9.38%) in the control group developed sensitization to dust mites. Logistic regression analysis confirmed an independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95% confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be treated to prevent sensitization in one child. CONCLUSION: Dust mite sensitization can be reduced in school age children with simple mite avoidance measures.

Air Pollution, Indoor↗
PubMed2002

The prevalence of asthma and wheezing illnesses amongst 10-year-old schoolchildren.

Asthma and wheezing illnesses carry a significant burden of disease during childhood. Prevalence studies have the capacity to provide invaluable insights into the nature of these common conditions. As part of the Isle of Wight Whole Population Birth Cohort Study (n=1456) we have examined wheezing and asthma development amongst 10-year-old children. At this age 1373 children completed ISAAC written questionnaires whilst 1043 children performed further testing including skin-prick testing, serum inhalant IgE antibody screening, spirometry and bronchial challenge. At 10-years, prevalence of current wheeze was 18.9%, current asthma (symptomatic bronchial hyper-responsiveness--BHR) 14.4% and currently diagnosed asthma (current wheeze and asthma ever--CDA) 13.0%. Both wheezing and asthma at 10 years were associated with average symptom onset at 3 years of age indicating an early life origin for such conditions. Current wheeze (P=0.011) and CDA (P=0.008) showed significant male predominance. Considerable disease morbidity was identified for these states that tended to be greatest amongst children defined asthmatic rather than simply current wheezers. Wheezing and asthma were significantly associated with both atopy (P<0.001) and allergic co-morbidity Children with these states, particularly current asthma, also demonstrated impaired lung function (FEV1, P<0.001 and FEV1/FVC, P=0.010) and increased BHR (inverse slope, P<0.001). In conclusion, Asthma and wheezing showed substantial prevalence at 10 years of age. Strong associations to male gender, atopy, impaired lung function and BHR were seen for both wheeze and asthma. In regard to prevalence and morbidity characteristics, a questionnaire-based definition of currently diagnosed asthma gave similar results to the use of symptomatic BHR in defining current asthma.

Age of Onset↗
PubMed2002

Rhinitis in 10-year-old children and early life risk factors for its development.

AIM: To study the prevalence, characteristics of and risk factors for childhood rhinitis. METHODS: In a whole population birth cohort study (n = 1,456) the prevalence and characteristics of rhinitis among 10-y-old children were examined. At this age 1373 children (94%) completed standardized questionnaires, 1,043 (72%) skin-prick testing, 953 (65%) serum inhalant immunoglobulin E antibody screening and 784 (54%) methacholine bronchial challenges. RESULTS: At the age of 10 y the prevalence of hayfever ever was 18.6% and current nasal symptoms (rhinitis) 22.6%. Rhinitis at 10 y was largely seasonal and associated with low morbidity, although 62.7% of cases required pharmacological treatment. Atopy (positive skin test) and other allergic states were associated with rhinitis (p < 0.001). Wheeze or diagnosed asthma was higher with coexistent rhinitis. Among wheezing children physician-diagnosed asthma (p < 0.024) and inhaled corticosteroid use (p < 0.001) were greater with the presence of rhinitis. Significant bronchial hyperresponsiveness (methacholine concentration giving a 20% fall in forced expiratory volume in I s <4.0 mg ml(-1)) was greater if rhinitis was present even when the child did not wheeze (p < 0.001). Risk factor analysis for rhinitis identified the independent significance for atopy (p < 0.001) and eczema (p = 0.009) at the age of 4 y plus paternal rhinitis (p < 0.001), maternal rhinitis (p = 0.033) and maternal food allergy (p = 0.016). CONCLUSION: Rhinitis is common at the age of 10 y, with strong associations with atopy, wheezing, asthma and bronchial hyperresponsiveness. An inherited predisposition towards atopy appears to predominate over environment in the aetiology of this state.

Bronchial Hyperreactivity↗
PubMed2001

Pharmacokinetics of andolast after administration of single escalating doses by inhalation in mild asthmatic patients.

The pharmacokinetics of andolast, a new tetrazolyl-benzamido derivative with antiallergic, antiinflammatory, mucosal protective and antisecretive activities, have been investigated in patients suffering from mild asthma (FEV(1) > or =70% of predicted) in whom obstruction was reversible (FEV(1) increase > or =15% of initial) after the administration of 0.2 mg of salbutamol by inhalation. Twelve out-patients (seven males and five females) were enrolled in the present study and were treated with a single dose of andolast of 2, 4 and 8 mg by inhalation using the MIAT Monohaler device according to a randomised crossover design. Plasma samples were collected before drug administration and up to 540 min after dosing. Andolast plasma concentrations were determined using a validated LC-MS/MS method with a limit of quantitation of 0.2 ng ml(-1). Pharmacokinetic analysis was carried out using standard non-compartmental methods. In addition, andolast safety and tolerability were evaluated by performing standard laboratory tests, by recording vital signs and ECGs and by monitoring the occurrence of adverse events throughout the study period. Andolast was absorbed after inhalation and was available to the systemic circulation. The mean peak plasma concentrations were 6.3, 10.9 and 30.5 ng ml(-1) at the three doses, respectively, and occurred at 30, 52.5 and 30 min (median t(max)). The mean AUC(t) values were 1852, 2889 and 7677 ng min ml(-1). The apparent plasma clearance (CL/F) and volume of distribution (V(z)/F) were, respectively, 1168 ml min(-1) and 430 l at the dose of 2 mg, 1143 ml min(-1) and 468 l at the dose of 4 mg, and 1141 ml min(-1) and 486 l at the dose of 8 mg. The apparent elimination half-life averaged 4.5, 5.0 and 4.6 h at the three doses, respectively. Even though the small number of subjects participating in the present study reduced the power of the statistical test, there was no statistically significant evidence of non-proportionality for all the andolast pharmacokinetic parameters calculated at the three doses. Thus, the data obtained as a whole suggest that andolast pharmacokinetics are dose-independent in the dose range investigated. Finally, the safety and tolerabilty of the drug administered to mild asthmatic patients was good up to the maximum investigated dose of 8 mg.

Administration, Inhalation↗
PubMed2001

Food allergen avoidance in primary prevention of food allergy.

Approximately 5-10% of children suffer from allergy to one or more foods. Primary prevention through a hypoallergenic diet may reduce the prevalence of food allergy and associated co-morbidity, such as eczema and urticaria. Breastfeeding has many advantages and should be recommended for all children. Those with a history of atopy in the immediate family are at a higher risk and maternal diet during lactation, avoiding highly allergenic foods, may enhance the benefit. Cow's milk should be strictly avoided, and supplements, if required, should be with a hypoallergenic formula. Delayed introduction of egg, nuts, wheat and fish has also been suggested. Dietary restriction may have nutritional consequences for the mother and child and supervision by a dietician is essential. Maternal diet during pregnancy is not advisable as the benefit is minimal and there may be adverse effects on the foetal nutrition. In high risk infants, a combined approach, where breastfeeding with maternal avoidance of highly allergenic foods, supplemented by extensively hydrolysed formula during the first 6 months of life, in addition to the delayed introduction of solid foods, has been shown to reduce the development of food allergy in infants.

Allergens↗