Drug-drug interaction database for safe prescribing of systemic antifungal agents.

INTRODUCTION: A drug-drug interaction (DDI) describes the influence of one drug upon another or the change in a drug's effect on the body when the drug is taken together with a second drug. A DDI can delay, decrease or enhance absorption or metabolism of either drug. Several antifungal agents have a large number of potentially deleterious DDIs. METHODS: The antifungal drug interactions database https://antifungalinteractions.org/was first launched in 2012 and is updated regularly. It is available as web and app versions to allow information on potential drug interactions with antifungals with a version for patients and another for health professionals. A new and updated database and interface with apps was created in 2019. This allows clinicians and patients to rapidly check for DDIs. The database is fully referenced to allow the user to access further information if needed. Currently DDIs for fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole, terbinafine, amphotericin B, caspofungin, micafungin and anidulafungin are cross-referenced against 2398 other licensed drugs, a total of nearly 17,000 potential DDIs. RESULTS: The database records 541 potentially severe DDIs, 1129 moderate and 1015 mild DDIs, a total of 2685 (15.9%). CONCLUSION: As the online database and apps are free to use, we hope that widespread acceptance and usage will reduce medical misadventure and iatrogenic harm from unconsidered DDIs.

Characterisation of fatigue and its substantial impact on health status in a large cohort of patients with chronic pulmonary aspergillosis (CPA).

INTRODUCTION: Fatigue is a prominent disabling symptom in several pulmonary diseases. Its impact on health status in patients with chronic pulmonary aspergillosis (CPA) has not been investigated. METHODS: A total of 151 CPA patients attending the National Aspergillosis Centre completed Manchester COPD Fatigue Scale (MCFS), St. George's Respiratory Questionnaire (SGRQ) and Medical Research Council (MRC) dyspnoea score. Lung function and BMI were measured. Univariate, multivariate linear and binary analyses, and principal component analysis (PCA) were used. RESULTS: Female patients accounted for 44%. The mean (range) of age was 59.6 (31-83) years, FEV1% was 64 (14-140), BMI was 23.6 (16.3-43.4), SGRQ total score was 56 (4-96.2) and MCFS total score was 30.6 (0-54). PCA showed that 27 items of MCFS loaded on three components; physical, psychosocial and cognitive fatigue, explaining 78.4% of fatigue variance. MCFS score correlated strongly with total SGRQ score (r = 0.83, p < 0.001). Using linear multivariate analysis, fatigue was the strongest factor (beta = 0.7 p < 0.0001) associated with impaired health status, after adjusting for age, BMI, FEV1%, and MRC dyspnoea score. Using patients' 5 self-assessment grades of their health, one-way ANOVA showed that those with "very poor" health status had the highest fatigue scores (45 (±6) (p < 0.001)). Logistic regression analysis showed that fatigue score (OR = 0.9, 95% CI 0.84-0.97; p = 0.005) and FEV1% (OR = 1.03, 95% CI 1.01-1.07, p = 0.02) are significantly associated with self-assessed impaired health status after correcting for age, gender and DLCO%. CONCLUSION: Fatigue is a major component of impaired health status of CPA patients.

Long-term antifungal treatment improves health status in patients with chronic pulmonary aspergillosis: a longitudinal analysis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an infectious disease that progressively destroys lung tissue. To date, no longitudinal data on the efficacy of antifungal treatment on health status in CPA patients exist. METHODS: Using the standardized St George's Respiratory Questionnaire, the health status of 122 patients with was assessed at baseline and quarterly over 12 months. The score range was 0-100, where higher score indicates worse heath status, and a change of ≥4 was deemed the minimal clinically important difference. Lung function, body mass index, Medical Research Council dyspnea scale, disease severity, and demographic data were reported. RESULTS: Mean age of patients was 59 years, and 45% were female. Overall, patients with CPA had substantial health status impairment at baseline. After treatment, 47%-50% gained substantial health improvement with a mean reduction of score of 14 at both 6 and 12 months, whereas 32% deteriorated with a mean rise of score of 11 and 14 after 6 and 12 months of treatment and observation, respectively, and 21% were not much different (stable). Patients gained therapeutic benefit irrespective of their illness severity where >50% of those who had "poor" and "very poor" status at baseline improved with score reduction of ≥4 after 6 months of treatment. Replicating this analysis using a health status category, we found that at least 50% of patients with a "poor/very poor" health status category at baseline improved significantly to "fair" or "good/very good" categories. Side effects burdened health status considerably. In multivariate analysis, dyspnea and disease severity significantly defined health status impairment. CONCLUSIONS: Antifungal therapy improved health status and prevented CPA progression in most patients.

Validity and reliability of the St. George's Respiratory Questionnaire in assessing health status in patients with chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) markedly reduces lung function through progressive lung destruction. To date, however, health status in patients with CPA has not been studied. This is due, in part, to a lack of adequately validated scales. The St. George's Respiratory Questionnaire (SGRQ) is widely used for several chronic respiratory diseases, but not for CPA. We examined the reliability and validity of SGRQ in CPA. METHODS: Eighty-eight patients with CPA completed the SGRQ, the Short Form-36 Health Survey (SF-36), and the Medical Research Council (MRC) dyspnea scale. Lung function and BMI were also measured. Pearson correlation, t test, analysis of variance, and their equivalents for nonparametric data and multivariate linear and binary analyses were used. RESULTS: The SGRQ components (symptoms, activity, and impact) and total scores achieved high internal consistency (Cronbach α = 0.77, 0.91, 0.86, and 0.94), and SGRQ components had good intercorrelation (r ≥ 0.41; P < .001) and correlated well with the total score (r ≥ 0.63; P < .001). There were high, intraclass, correlation coefficients for the total SGRQ and its dimensions (≥ 0.92). The SGRQ scores showed significant correlation with the MRC dyspnea scale and SF-36 components and differentiated between all grades of shortness of breath and different bands of disease severity (P < .05). In addition, patients with greater clinician-rated disease severity had more impairment of health status (P < .006). CPA severity was independently associated with impairment in health status, and COPD comorbidity significantly affected the health status in patients with CPA. CONCLUSIONS: SGRQ demonstrated a significant level of reliability and validity in measuring health status in CPA.

Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study.

RATIONALE: Some patients with severe asthma are immunologically sensitized to one or more fungi, a clinical entity categorized as severe asthma with fungal sensitization (SAFS). It is not known whether SAFS responds to antifungal therapy. OBJECTIVES: To evaluate the response of SAFS to oral itraconazole. METHODS: Patients with severe asthma sensitized to at least one of seven fungi by skin prick or specific IgE testing were recruited. All had total IgE less than 1,000 IU/ml and negative Aspergillus precipitins. They were treated with oral itraconazole (200 mg twice daily) or placebo for 32 weeks, with follow-up for 16 weeks. MEASUREMENTS AND MAIN RESULTS: The primary end point was change in the Asthma Quality of Life Questionnaire (AQLQ) score, with rhinitis score, total IgE, and respiratory function as secondary end points. Fifty-eight patients were enrolled, of whom 41% had been hospitalized in the previous year. Baseline mean AQLQ score was 4.13 (range, 1-7). At 32 weeks, the improvement (95% confidence interval) in AQLQ score was +0.85 (0.28, 1.41) in the antifungal group, compared with a -0.01 (-0.43, 0.42) change in the placebo group (P = 0.014). Rhinitis score improved (-0.43) in the antifungal, and deteriorated (+0.17) in the placebo group (P = 0.013). Morning peak flow improved (20.8 L/minute, P = 0.028) in the antifungal group. Total serum IgE decreased in the antifungal group (-51 IU/ml) but increased in placebo group (+30 IU/ml) (P = 0.001). No severe adverse events were observed, but seven patients developed adverse events requiring discontinuation, five in the antifungal group. CONCLUSIONS: SAFS responds to oral antifungal therapy as judged by large improvements in quality of life in about 60% of patients.

Aspergillus genomes and the Aspergillus cloud.

Aspergillus Genomes is a public resource for viewing annotated genes predicted by various Aspergillus sequencing projects. It has arisen from the union of two significant resources: the Aspergillus/Aspergillosis website and the Central Aspergillus Data REpository (CADRE). The former has primarily served the medical community, providing information about Aspergillus and associated diseases to medics, patients and scientists; the latter has focused on the fungal genomic community, providing a central repository for sequences and annotation extracted from Aspergillus Genomes. By merging these databases, genomes benefit from extensive cross-linking with medical information to create a unique resource, spanning genomics and clinical aspects of the genus. Aspergillus Genomes is accessible from http://www.aspergillus-genomes.org.uk.