Management of pulmonary exacerbations in cystic fibrosis: still an unmet medical need in clinical practice.

Pulmonary exacerbation (PEx) is a hallmark of cystic fibrosis. Although several criteria have been proposed for the definition of PEx, no consensus has yet been reached. Very often, many PEx cases go unreported. A standardized and validated definition is needed to reduce variability in clinical practice. The pathophysiology of recurrent episodes remains unclear, and both onset and risk are multifactorial. PEx leads to increased healthcare costs, impaired quality of life and a cycle in which PEx causes loss of lung function, which predisposes to further episodes. The number of episodes affects survival. Although early diagnosis and aggressive treatment are highly recommended, measures to prevent the emergence of new PEx are even more important. In particular, inhaled antibiotics administered under new treatment schedules could play a key role in preventing exacerbations and thus delay decline in lung function and reduce mortality. The primary objective is zero exacerbations.

Validation of the first treatment-specific questionnaire for the assessment of patient satisfaction with allergen-specific immunotherapy in allergic patients: the ESPIA questionnaire.

BACKGROUND: Satisfaction with treatment is a patient-reported outcome shown to be associated with the patient's health-related decisions and treatment-related behavior, thereby influencing the chances of successful treatment, and is especially relevant in long-term treatment, such as allergen-specific immunotherapy (AIT). OBJECTIVE: We sought to assess the psychometric properties of the Satisfaction Scale for Patients Receiving Allergen Immunotherapy (ESPIA) questionnaire so as to determine the satisfaction of patients receiving AIT treatment. METHODS: An observational, longitudinal, multicenter study was performed on patients with allergic rhinitis (AR) undergoing AIT treatment. Sociodemographic, clinical, and patient-centered health outcomes data were gathered at the study visits. Feasibility, reliability, validity, and sensitivity to change of the prevalidated version of the ESPIA questionnaire were assessed. RESULTS: Four hundred twenty-nine patients were included (52.2% women, 33.6 years of age, 54.5% of the cases with intermittent AR and 62.5% with moderate AR). Low levels of missing items and ceiling/floor effects were found for the overall score of the ESPIA questionnaire. The overall Cronbach α value and intraclass correlation coefficient were 0.90 and 0.92, respectively. The overall score for the ESPIA questionnaire was strongly associated with months receiving AIT, AR type and intensity, presence of conjunctivitis, self-perceived health status, effect of AR on daily life, and expectations about the AIT treatment. The pattern of correlations obtained with other patient-centered health outcomes was consistent with expectations. The ESPIA questionnaire also showed good sensitivity to change for improved health status. CONCLUSION: The ESPIA questionnaire to assess patient satisfaction with respect to AIT treatment presented satisfactory psychometric properties for its use in clinical practice.

Development of a questionnaire to assess patient satisfaction with allergen-specific immunotherapy in adults: item generation, item reduction, and preliminary validation.

BACKGROUND: Allergen-specific immunotherapy (SIT) is a treatment capable of modifying the natural course of allergy, so ensuring good adherence to SIT is fundamental. Up until now there has not existed an instrument specifically developed to measure patient satisfaction with SIT, although its assessment could help us to comprehend better and improve treatment adherence and effectiveness. The aim of this study was to develop an instrument to measure adult patient satisfaction with SIT. METHODS: Items were generated from a literature review, focus groups with allergic adult patients undergoing SIT, and a meeting with experts. Potential items were administered to allergic patients undergoing SIT in an observational, cross-sectional, multicenter study. Item reduction was based on quantitative and qualitative criteria. A preliminary assessment of feasibility, reliability, and validity of the retained items was performed. RESULTS: An initial pool of 70 items was administered to 257 patients undergoing SIT. Fifty-four items were eliminated resulting in a provisional instrument with 16 items. Factor analysis yielded four factors that were identified as perceived efficacy, activities and environment, cost-benefit balance, and overall satisfaction, explaining 74.8% of variance. Ceiling and floor effects were negligible for overall score. Overall score was associated with the type and intensity of symptoms. CONCLUSION: This is the first attempt to develop a satisfaction with SIT measure from the perspective of the allergic patient, and evidence has been found in favor of its reliability and validity.

Observational study of the safety of an ultra-rush sublingual immunotherapy regimen to treat rhinitis due to house dust mites.

BACKGROUND: Ultra-rush regimens for administering sublingual immunotherapy to patients with allergies are becoming more widespread. We aimed to assess treatment safety for patients with allergic rhinitis with or without asthma caused by Dermatophagoides house dust mites. METHODS: This observational study at 5 Spanish centers included 218 patients aged 4-64 years, of whom 117 were women and 122 were under 15 years old. Ultra-rush regimen consisted of incremental doses of an allergen extract comprising a 50% mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae (30, 60, 120, 240 IR every 30 min) followed by maintenance therapy. Adverse reactions were monitored and asthmatic patients underwent spirometric testing at baseline and after each dose. Follow-up was scheduled after 2 weeks of maintenance with 240 IR three times a week. RESULTS: Five patients had to modify ultra-rush regimen because of mild local adverse reactions. In total, 32 adverse reactions were reported in 27 patients during the ultra-rush regimen. Seven of these events were local gastrointestinal reactions, and the remaining 17 were local reactions, mainly labial or mouth itching and burning. Eight events were systemic reactions [rhinitis (n = 3), general malaise (n = 1), general malaise and vomiting (n = 1), dizziness (n = 1), asthma (n = 1), dyspnea (n = 1)]. All adverse reactions were mild or moderate. Serious adverse events or life-threatening anaphylactic reactions were not reported. CONCLUSIONS: High-dose sublingual immunotherapy with Dermatophagoides allergen extracts can be safely administered in an ultra-rush regimen, although its usefulness and benefit for perennial allergens (e.g. house dust mites) must be evaluated.

Development of an allergen extract for sublingual immunotherapy--evaluation of Staloral.

BACKGROUND: Specific immunotherapy (IT) is an effective treatment for rhinitis and asthma caused by aeroallergens sensitization. Sublingual IT (SLIT) was introduced to solve the problem of systemic reactions to subcutaneous IT (SCIT) and developed to represent an actual treatment option. It is now generally accepted that allergen doses much higher than those administered by SCIT must be used to achieve clinical efficacy on allergic symptoms. OBJECTIVE: To evaluate the characteristics of Staloral, an allergen extract produced by Stallergenes (Antony, France) in terms of practical administration, efficacy, safety and mechanism of action. METHODS: Data were obtained from 20 double-blind, placebo-controlled studies using Staloral in patients sensitized to pollens and house-dust mites, and also from open studies concerning practical administration and the mechanism of action. RESULTS/CONCLUSION: Efficacy and safety of Staloral, as demonstrated by the revision of the studies, which used doses up to 1125 times those administered with SCIT, are very satisfactory and confer to this allergen extract optimal characteristics for treating patients with seasonal allergies due to pollens or with perennial symptoms induced by dust mites. The main mechanism of action is the interaction with dendritic cells of the oral mucosa and the subsequent tolerance induced in T cells.

Systemic tolerability of specific subcutaneous immunotherapy with index-of-reactivity-standardized allergen extracts administered using clustered regimens: a retrospective, observational, multicenter study.

BACKGROUND: Subcutaneous immunotherapy is an etiological therapy for certain IgE-mediated diseases. It is usually administered in 2 phases: induction and maintenance. Administration in clustered schedules during the induction phase may be a valid alternative to reach the maintenance dose early if the treatment is well tolerated. OBJECTIVES: To compare the tolerability of different clustered schedules in subcutaneous immunotherapy with standardized allergen extracts administered and to identify factors associated with increased risk of systemic reactions (SRs). METHODS: Retrospective, observational, multicenter study in patients with allergic respiratory disease. RESULTS: Data from 1,147 patients were collected. Thirty-nine patients (3.4%) experienced 42 SRs (0.6% of doses). According to the European Academy of Allergy and Clinical Immunology SR grading system, there were 7 grade 0 reactions (16.7%), 26 grade 1 reactions (61.9%), 8 grade 2 reactions (19.0%), and 1 grade 3 reaction (2.4%). There were no grade 4 SRs (anaphylactic shock). We observed a higher risk of SRs in patients who received an initial dose higher than 0.3 index of reactivity (IR); only 2 reactions occurred after administration of the initial dose of the regimen, both with 0.4 IR. The remainder appeared in subsequent injections, although never with a dose lower than 0.35 IR. CONCLUSIONS: Clustered regimens with IR-standardized extracts are an alternative to classic immunotherapy thanks to their low incidence of SRs compared with other rapid regimens during the induction phase. The ideal clustered regimen should start at an initial dose no greater than 0.35 IR to minimize the incidence of SRs.