A new instrument for assessing quality of life in atopic dermatitis: international development of the Quality of Life Index for Atopic Dermatitis (QoLIAD).

BACKGROUND: Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that can have a considerable impact on those affected. There are a number of instruments available to measure outcome in dermatological conditions but none have been developed specifically for AD. In addition, most measure symptoms and/or daily functioning, which are potential influences on quality of life (QoL) rather than assessments of the construct itself. OBJECTIVES: The aim of the current study was to develop a new instrument specifically designed to measure QoL in adults with AD-the Quality of Life Index for Atopic Dermatitis (QoLIAD). METHODS: The instrument was developed based on the needs-based model of QoL and was produced in several different countries simultaneously. Its content was derived from 65 in-depth interviews with relevant patients in the U.K., Italy and the Netherlands. The initial version of the measure was produced in U.K. English and translations were produced for the Netherlands, Italy, Germany, France and the U.S.A. using a dual translation panel methodology. A Spanish version was developed using the same adaptation process after the instrument was finalized. Field-test interviews were conducted with approximately 20 patients in each country to assess face and content validity. The instrument [in addition to the Dermatology Life Quality Index (DLQI) and the Psychological General Well-Being Schedule (PGWB)] was then administered to up to 300 AD patients in each country at two time points to finalize the instrument and test its psychometric properties. RESULTS: The initial version of the QoLIAD had 56 items that reflected the areas of need fulfillment identified in the qualitative interviews as having been affected by AD: mental and emotional stimulation, physical and emotional stability, security, sharing and belonging, self-esteem, personal development and fulfillment. Comments from patients in field-test interviews resulted in the removal of 14 items, to leave a 42-item instrument that was considered relevant and acceptable. The number of patients participating in the survey were 286 in the U.K., 46 in the Netherlands, 213 in France, 187 in Germany, 178 in the U.S.A. and 83 in Spain. Application of the Rasch model to these data identified the final 25-item QoLIAD. Unidimensionality was confirmed, with deviation of the total scale from the Rasch model evident at a single time point in one country only (the U.K.). All language versions, with the exception of the Dutch measure, had test-retest reliability coefficients in excess of 0.85. The test-retest in the Netherlands was 0.80. However, this country had the smallest sample size and the corresponding reliability for the DLQI was only 0.40. The QoLIAD had adequate internal consistency and the initial indications of construct validity were good. The levels of association with the DLQI indicated that the two instruments measure related but distinct constructs. CONCLUSIONS: The QoLIAD is a practical, reliable, valid and culturally applicable instrument for measuring the impact of AD and its treatment on QoL in clinical trials or in routine clinical practice.

Therapeutic equivalence of inhaled beclomethasone dipropionate with CFC and non-CFC (HFA 134a) propellants both delivered via the Easibreathe inhaler for the treatment of paediatric asthma.

Chlorofluorocarbon (CFC)-containing inhalers for use in the treatment of asthma are to be phased out under the terms of the Montreal Protocol (1). In this multi-centre, randomized, double-blind study, the therapeutic equivalence of two formulations of beclomethasone dipropionate (BDP) containing CFC or non-CFC (HFA134a) propellant, both delivered via the Easibreathe (Norton Healthcare Ltd, London, U.K.) inhaler, was determined in 229 asthmatic children. Each child received 100 microg doses of BDP (containing either CFC or HFA propellant) twice daily for 12 weeks. Both CFC and HFA formulations produced statistically and clinically significant improvements in patient's lung function and symptom scores when administered via the Easibreathe inhaler. The improvements in mean morning peak expiratory flow (PEF) were 41 l min(-1) and 34 l min(-1) for the BDP-HFA and BDP-CFC products respectively (P<0.001) and for mean evening PEF the improvements were 38 l min(-1) and 38 l min(-1), respectively (P<0.001). Similar findings were demonstrated for the other efficacy parameters. The two formulations were statistically equivalent with respect to efficacy. For mean morning PEF the estimated treatment difference (BDP-CFC/BDP-HFA ratio) was 102.6% (95% CI 99.1, 106.2). Similar equivalence was shown for the other efficacy parameters. Both products were well tolerated, with no difference in the adverse event profiles, effects on 24 h urinary cortisol or Candida colonisation. This study demonstrates that the new formulation of BDP with HFA-134a propellant is equivalent to and directly substitutable for BDP with the older CFC propellant in a dose for dose manner. This should enable a seamless transition from one product to the other when CFC containing products are eventually phased out. In addition this study has also shown that the Easibreathe inhaler is an effective delivery system for use with inhaled products for the treatment of asthma in children.

Effect of nitrogen dioxide and sulphur dioxide on airway response of mild asthmatic patients to allergen inhalation.

Air pollution may enhance the airway response of asthmatic subjects to allergen inhalation. To test the hypothesis that sulphur dioxide and nitrogen dioxide alone or in combination could have a contributory role, we have studied the effect of 6 h exposure to air, 200 parts per billion (ppb) sulphur dioxide, 400 ppb nitrogen dioxide, and the two gases together on the airway response to inhaled allergen in ten volunteers with mild atopic asthma. The subjects were exposed to the gases in random order at weekly visits, then challenged with pre-determined concentrations of Dermatophagoides pteronyssinus allergen 10 min after each exposure. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and cumulative breath units (CBU) of D pteronyssinus allergen required to produce a 20% fall in FEV1 (PD20FEV1) were measured after each exposure. Compared with air, neither sulphur dioxide nor nitrogen dioxide nor the combination significantly altered FEV1 or FVC. Although the decreases in PD20FEV1 after exposure to each agent alone were not significant (41.2%, p = 0.125 after nitrogen dioxide; 32.2%, p = 0.506 after sulphur dioxide) the decrease after exposure to the combination was significant (60.5 [SE 8.1]%, p = 0.015). Exposure to a combination of sulphur dioxide and nitrogen dioxide in concentrations that could be encountered in heavy traffic enhances the airway response to inhaled allergen, possibly as a result of previous airway inflammation.

Comparison of a new antihistaminic and antiallergic compound KW 4679 with terfenadine and placebo on skin and nasal provocation in atopic individuals.

The effects of three oral doses of a new compound KW 4679 thought to have both antihistaminic and antiallergic properties were compared with terfenadine and placebo in a double-blind cross-over trial in 15 volunteers with seasonal allergic rhinitis. Comparison of the effect of the treatments with either 2.5, 5 or 10 mg b.i.d. of KW 4679, 60 mg b.i.d. of terfenadine or placebo was made on the response to histamine and grass pollen skin-prick testing. Nasal provocation testing with grass pollen was performed on the eighth day of treatment. Nasal airway resistance (NAR) was measured using active posterior rhinomanometry and the dose of grass pollen which caused a 200% increase in NAR was determined. The number of sneezes in the first 12 min was counted. Compared with placebo all doses of KW 4679 and terfenadine significantly inhibited the skin weal response to histamine and grass pollen (P < 0.001). The inhibitory effect of KW 4679 on both histamine and allergen induced skin weals was significantly greater than that of terfenadine (P = 0.001 and P = 0.049 respectively). The results of nasal challenges with grass pollen showed that all doses of KW 4679 and terfenadine were effective in reducing sneeze counts (P < 0.001), though there were no significant effects on allergen induced increase in NAR. All three doses of KW 4679 were generally well tolerated. Drowsiness was reported by some of the volunteers on KW 4679 and one volunteer reported drowsiness whilst taking placebo. Slight and reversible rises in AST and ALT concentrations were observed; these were not considered clinically significant.

Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma.

The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.

Factors affecting the long-term variability of bronchial responsiveness in an adult general practice population.

There have been few longitudinal studies of bronchial responsiveness. We wanted to assess the long-term variability and associations of bronchial responsiveness in the general population. Spirometry, bronchial provocation tests, skin-prick tests for allergy, and respiratory symptom questionnaires were repeated every 4 months, for 2 years (August 1987-August 1989), in 122 volunteers recruited from a cross-sectional survey of population. Provocation dose producing a 20% fall in forced expiratory volume in one second (PD20FEV1) and dose-response slope (SL), which gives values for methacholine responsiveness, were measured in all subjects. SL correlated well with PD20FEV1 but repeatability was impaired in those subjects with unmeasurably high PD20FEV1. The 95% range for repeatability of PD20FEV1 was +/- 3.11 doubling doses and +/- 4.52 doubling slopes for SL. Bronchial responsiveness increased in those with self-reported colds and reduced FEV1 in winter 1987-1988, and in males in winter 1988-1989. Bronchial responsiveness increased during the summer (June-August) of both years, significantly in year 1. We conclude that bronchial responsiveness showed minor seasonal variability and that colds were the strongest predictors of increased bronchial responsiveness over the 2 yr period.

The effect of salbutamol controlled release on airways responsiveness to inhaled methacholine in mild asthmatic subjects.

Single doses of inhaled bronchodilating agents have been shown to reduce airways responsiveness (AR) in both normal and asthmatic individuals. The longer term effects of these treatments on airways responsiveness are less clear. We have studied the effects of 4 weeks of treatment with oral salbutamol controlled release (SCR) (8 mg b.d.) on airways responsiveness in mild asthmatics in a double-blind, placebo-controlled study. Airways responsiveness to inhaled methacholine, baseline FEV1 and plasma salbutamol levels was assessed 6 h, 48 h and 4 weeks after commencing treatment and again 24 h and 72 h after cessation of medication. When compared to placebo, SCR significantly attenuated AR at the 48-h time point only. There were no increases in AR recorded at any of the post-treatment time points. In addition, there were no significant differences in baseline FEV1 at any of the time-points studied, when compared to placebo. The change in AR at 48 h after starting treatment was probably due to functional antagonism of smooth muscle contraction. Importantly, there were no increases in AR recorded at either of the post-treatment time points.

A double-blind comparison of the effects of cefaclor and amoxycillin on respiratory tract and oropharyngeal flora and clinical response in acute exacerbations of bronchitis.

Fifty-one patients admitted to hospital with severe exacerbations of chronic bronchitis entered a double-blind trial of treatment with cefaclor (500 mg tds) compared with amoxycillin (500 mg tds) for 7 days. Twenty-six patients received cefaclor and 25 amoxycillin. Sputum and throat swabs were collected on admission, after 7 days of therapy and at outpatient follow-up, 3 weeks after treatment had finished. Clinical status and spirometry were assessed on admission and at the third, seventh and 28th day. There was no significant difference between the two regimes for clinical outcome, spirometry or numbers of infecting pathogens. Opportunistic colonization with resistant Gram-negative organisms and Candida species was highly prevalent on admission (56%) in both groups, perhaps because of previous antibiotic administration and general debility of the majority of patients. The high prevalence of opportunistic colonizing organisms persisted at follow-up (48%) with a significant excess of new organisms (Enterobacter cloacae, Klebsiella species and Candida species) present in sputum in the amoxycillin-treated patients. Cefaclor may be less damaging to normal flora than amoxycillin with a consequently reduced risk of colonization and superinfection of the respiratory tract with resistant Gram-negative organisms and yeasts.

The daily variability of bronchial responsiveness to methacholine.

Ten mild atopic asthmatics on inhaled beta 2-agonists alone were studied in order to determine the repeatability of methacholine inhalation provocation tests at 24 h intervals over a period of 5 days. Such patients are most frequently studied in therapeutic trials of anti-asthmatic medications. There were no significant differences in results obtained on any of the days and no evidence for the development of tolerance to methacholine in this group of patients at one day intervals. The 95% confidence interval for repeatability of the results was +/- 1.05 doubling doses of methacholine, and 95% range +/- 2.36 doubling doses, comparable to the results obtained by other investigators on similar patients. Some investigators have produced more highly repeatable results but these have generally been obtained using highly selected groups of patients.