Treatment of the recalcitrant asthmatic

Treatment of "difficult" asthma requires good doctor-patient communication, patient education, and attention to precipitating factors as well as an aggressive drug regimen. Specific medications include inhaled sympathomimetic and anti-cholinergic bronchodilators, inhaled, oral and/or intravenous corticosteroids and, in certain circumstances, mast cell stabilizing drugs such as cromolyn sodium. The use of systemic theophyllines is currently undergoing critical reevaluation. There have been a number of recent developments in the search for steroid-sparing agents and drugs that inhibit inflammatory mediators felt to be important in the pathophysiology of asthma. Most of these drugs are still undergoing evaluation in multicentre clinical trials. The newer antiinflammatory agents, methotrexate and gold, should probably not be used on a routine basis except as part of randomized, ethically approved clinical trials.     

Direct clinician-to-patient feedback discussion of inhaled steroid use: its effect on adherence.

STUDY OBJECTIVES: To evaluate whether direct feedback discussion on inhaled steroid use might influence subsequent adherence with this therapy. DESIGN AND SETTING: A 10-week, single-blind, randomized trial in asthma patients. Inclusion criteria included forced expiratory volume in 1 second <80%, one or more markers for low socioeconomic status, and the use of inhaled steroids. Inhaled steroid and beta-agonist use were electronically monitored. All patients received standard asthma care. The treatment group received direct clinician-to-patient feedback discussion on their inhaled steroid and beta-agonist use on all subsequent visits, whereas this information was withheld during the study period in the control group. MEASURES: 1) Mean weekly inhaled steroid adherence [(number of actuations/prescribed number of actuations) x 100]; 2) number of days with overuse of inhaled steroids; 3) 24-hour and nighttime albuterol use; 4) included forced expiratory volume in 1 second; and 5) Asthma Quality of Life Questionnaire total score. RESULTS: Ten treatment and nine control patients completed the study. Mean weekly inhaled steroid adherence over the first week was not significantly different in the treatment and control groups: 61 +/- 9% versus 51 +/- 5%, respectively. However, by the second week, adherence increased to 81 +/- 7% in the treatment group, whereas it decreased to 47 +/- 7% in the control group (P = 0.003). Adherence remained above 70% in the treatment group for the entire trial, but continued to decrease in the control group. Overuse of inhaled steroids was low in both groups. There were no group differences in any of the asthma outcomes. CONCLUSIONS: Direct clinician-to-patient feedback discussion on inhaled steroid use using electronic printouts did improve adherence in the short-term in asthma patients at high-risk for poor adherence.     

Medication adherence as a learning process: insights from cognitive psychology

Non-adherence to medications is one of the largest contributors to sub-optimal health outcomes. Many theories of adherence include a ‘value–expectancy’ component in which a patient decides to take a medication partly based on expectations about whether it is effective, necessary, and tolerable. We propose reconceptualising this common theme as a kind of ‘causal learning’ – the patient learns whether a medication is effective, necessary, and tolerable, from experience with the medication. We apply cognitive psychology theories of how people learn cause–effect relations to elaborate this causal-learning challenge. First, expectations and impressions about a medication and beliefs about how a medication works, such as delay of onset, can shape a patient’s perceived experience with the medication. Second, beliefs about medications propagate both ‘top-down’ and ‘bottom-up’, from experiences with specific medications to general beliefs about medications and vice versa. Third, non-adherence can interfere with learning about a medication, because beliefs, adherence, and experience with a medication are connected in a cyclic learning problem. We propose that by conceptualising non-adherence as a causal-learning process, clinicians can more effectively address a patient’s misconceptions and biases, helping the patient develop more accurate impressions of the medication.     

Caring for adolescents with HIV

Adolescents comprise a growing proportion of people diagnosed with HIV or AIDS. Navigating adolescence while infected with HIV presents specific challenges not only to the youth but to their families and caregivers. As children enter their teen years, they have medical, physiologic, and psychosocial issues that differ greatly from both younger children and young adults. These issues include the limited number of medications available, mental illness (especially depression), and psychosocial issues such as distorted body image, sexual awareness, and problems with family and peer relations. Many of these issues are heightened in this population and can be important factors that can influence adherence. Awareness of these issues is important for health care providers, for if they understand not just the illness itself, but the psychosocial issues of the patient they are treating, the clinician can optimize treatments and adherence, and help these young persons successfully transition into adulthood.     

Exercise-induced asthma: diagnosis and management.

OBJECTIVE: To review the diagnosis and management of exercise-induced asthma (EIA). DATA SOURCES: Computer-assisted literature searches on MEDLINE for articles, abstracts, and other relevant data on exercise-induced asthma STUDY SELECTION: Published articles, abstracts, and conference proceedings were selected. RESULTS: EIA is seen in 40 to 90% of asthmatic patients. Exercise can be the sole trigger or be one of multiple triggers of asthma exacerbations. A good history and physical examination can diagnose most cases of EIA. Spirometry can confirm the diagnosis. Exercise testing may be necessary in certain cases. Prevention through both pharmacologic and nonpharmacologic measures is the key to EIA management. Inhaled beta-agonists remain the medications of choice for EIA prophylaxis. Inhaled cromolyn and antileukotrienes are alternatives. Good long-term control of asthma with anti-inflammatory medications such as inhaled steroids will also decrease the incidence of EIA. CONCLUSIONS: Early diagnosis and proper preventive and maintenance therapy can reduce episodes of EIA and enable patients to continue to engage in sports and lead an active life.     

Measuring adherence to antiretroviral medications in clinical trials

Antiretroviral medications have the potential to transform HIV infection from a fatal to a chronic disease. One of the significant barriers to clinical success is medication nonadherence. Measuring adherence in clinical trials is increasingly important because inadequate adherence may explain some of the variation in clinical response in antiretroviral clinical trials. Additionally, to quantitate the success of interventions that improve adherence, accurate measures need to be utilized. This article summarizes commonly used adherence measures in HIV clinical trials and observational studies such as patient self-report, pill counts, plasma levels, and electronic monitoring. The merits and shortcomings of each measure are discussed.     

Measurement of children's asthma medication adherence by self report, mother report, canister weight, and Doser CT.

BACKGROUND: Accurate assessment of medication adherence has been difficult to achieve but is essential to drug evaluation in clinical trials and improved outcomes in clinical care. OBJECTIVE: This study was conducted to compare four adherence assessment methods: child report, mother report, canister weight, and electronic measurements of metered dose inhaler (MDI) actuation. METHODS: Participants included 27 children with mild-to-moderate asthma who were followed prospectively for 6 months. All patients used an MDI equipped with an electronic Doser attached to their inhaled steroid. At each 2-month follow-up visit, Doser and canister weight data were recorded, while child and mother were interviewed separately regarding medication use. RESULTS: Children and mothers reported, on average, over 80% adherence with the prescribed inhaled steroid. Canister weight revealed, on average, adherence of 69%, significantly lower than self-report. When adherence recorded by the electronic Doser was truncated to no more than 100% of prescribed daily use, average adherence was 50%. Older children and adolescents, nonwhite children, and those from poorer functioning families were least adherent. CONCLUSIONS: Electronic adherence monitoring was significantly more accurate than self-report or canister weight measures. Such accuracy is an essential prerequisite to increasing understanding of the treatment, setting, and patient factors that influence adherence, and to the consequent design of effective intervention strategies.     

Physician estimates of adherence and the patient-physician relationship as a setting to improve adherence to antiretroviral therapy

Physicians estimate their patients' adherence to medications, and base decisions about treatment on these estimates. In HIV, misjudgment of patient adherence can have adverse consequences, including withholding of therapy, unnecessary changes in therapy, or unnecessary laboratory testing. A review of the literature demonstrates that physicians are often inaccurate in estimating patient adherence with antiretroviral therapy. These findings have implications for practice. Standardized methods for adherence assessment are currently available that can be used to enhance physicians' ability to understand adherence behavior and barriers. The patient-physician relationship presents a unique setting for improving adherence. The authors propose interventions to improve adherence within the context of the patient-physician relationship at the physician level, interpersonal level, and organizational level. Improved communication, including discussion about patient lifestyle and preferences, can facilitate a frank exchange of information, negotiation, and a spirit of cooperation. Active patient participation in the decision-making process is crucial.     

Qualitative research-enhanced understanding of patients' beliefs: results of focus groups with low-income,urban, African American adults with asthma

BACKGROUND: Qualitative research is an important research methodology for understanding the health beliefs and attitudes of patients. These beliefs and attitudes have been proposed as partial explanations for low adherence to medical therapy and the consequent high burden of morbidity from asthma among low-income urban minorities. OBJECTIVE: The purpose of this study was to explore barriers to adherence to inhaled corticosteroids (ICSs), health beliefs regarding asthma and its treatment, and opinions about providers and clinical research among low-income groups. METHODS: Three focus groups were conducted with 15 low-income, urban, African American adults with persistent asthma. These focus group sessions were audiotaped, transcribed verbatim, and coded by using qualitative analytic techniques. RESULTS: Health beliefs that influenced adherence included patients' reliance on their assessment of asthma control over that of the health provider and concern over the adverse effects of ICS therapy. Adherence was also adversely affected by social obligations and insurers' approval policies and restricted formularies. Although mistrust of the medical establishment was evident, members generally expressed a willingness to participate in nonpharmacologic clinical research and the belief that research was beneficial. However, they had strong preferences for where the research should be conducted. CONCLUSIONS: Although barriers exist to ICS adherence in patient populations, many of these can be addressed during patient-clinician interactions. Qualitative research is an important tool for formulating hypotheses for improving ICS adherence that can then be tested in the future by using quantitative research methods.     

Need for theophylline in severe steroid-requiring asthmatics

Concern about side-effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi-medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti-asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in-patients, 12–15 years old, completed a double-blind, cross-over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long-acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10–30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids.     

Childhood asthma: new insights into management.

Recently, a concerted effort has been made to reverse the trend of increasing asthma mortality and morbidity. One additional strategy might be to recognize patients at risk for persistent asthma and to intervene early. This review summarizes new information on asthma pathogenesis that has helped shape a new direction in managing childhood asthma. At the core is the recognition that asthma is a chronic inflammatory disease. Subsequently, inhaled steroids, the most potent anti-inflammatory asthma medications, have emerged as the cornerstone of the management of persistent asthma. The recent report of the National Heart, Lung, and Blood Institute's Childhood Asthma Management Program provides a comprehensive "profile of performance" for 3 treatment choices for the management of persistent asthma. This study answers questions regarding the benefits and shortcomings of the medications evaluated and prompts a closer evaluation of the long-term effects of other treatment strategies, including medications currently being developed. Although intervention with inhaled steroids offers new opportunities to control the development of asthma, one must be cognizant of potential risks in early and long-term therapeutic intervention. This review provides a perspective on our present knowledge, the rationale for early intervention, and opportunities for more aggressive therapy, as well as speculation on how ongoing clinical research will continue to play a role in advancing asthma care and moving toward a "cure" for this life-threatening disease.     

Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone.

BACKGROUND: Inhaled steroids such as fluticasone propionate and beclomethasone dipropionate play a central role in the treatment of bronchial asthma. Fluticasone exhibits excellent clinical effectiveness; however, oral adverse effects can occur. OBJECTIVE: To compare the frequency of oral candidiasis in asthmatic patients treated with fluticasone and beclomethasone, to evaluate the effect of gargling with amphotericin B, and to measure the inhalation flow rate on candidiasis. METHODS: The study consisted of 143 asthmatic patients who were treated with inhaled steroids, 11 asthmatic patients not treated with inhaled steroids, and 86 healthy volunteers. Quantitative fungal culture was performed by aseptically obtaining a retropharyngeal wall swab from these patients. Patients with positive results were treated with gargling using a 1:50 dilution amphotericin B solution. In asthmatic patients treated with fluticasone, the inhalation flow rate was measured using an inspiratory flow meter. RESULTS: The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone. Gargling with amphotericin B was effective in most asthmatic patients with candidiasis. Candidiasis was not due to inappropriate flow rates during inhalation of steroids. CONCLUSIONS: Fungal culture of a retropharyngeal wall swab may be useful for predicting the risk of developing oral candidiasis in asthmatic patients treated with inhaled steroids. The amount of isolated Candida was significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Attention to dosage is required as the amount of Candida increased with dose of fluticasone. Gargling with a 1:50 dilution of amphotericin B is effective in treating oral candidiasis of asthmatic patients treated with inhaled steroids.     

Monitoring adherence to beclomethasone in asthmatic children and adolescents through four different methods

Background:  Suboptimal adherence to inhaled steroids is a known problem in children and adolescents, even when medications are administered under parental supervision. This study aimed to verify the adherence rate to beclomethasone dipropionate (BDP) by four currently available methods.
Methods:  In this concurrent cohort study, 102 randomly selected asthmatic children and adolescents aged 3–14 years were followed for 12 months. Adherence rate was assessed every 2 months by self and/or parent report, pharmacy dispensing data, electronic device (Doser^®; Meditrack Products, Hudson, MA, USA) monitor, and canister weight.
Results:  Mean adherence rates to BDP by self and/or parent report, pharmacy records, Doser, and canister weight were 97.9% (95% CI 88.0–98.6), 70.0% (95% CI 67.6–72.4), 51.5% (95% CI 48.3–54.6), and 46.3% (95% CI 44.1–48.4), respectively. Agreement analysis between (Doser) and canister weight revealed a weighted kappa equal to 0.76 (95% CI 0.65–0.87).
Conclusions:  Adherence was a dynamic event and rates decreased progressively for all methods over the 12-month follow-up. Canister weight and electronic monitoring measures were more accurate than self/parent reports and pharmacy records. Rates obtained by these two methods were very close and statistical analysis also showed a substantial agreement between them. As measurements by canister weight are less costly compared with currently available electronic devices, it should be considered as an alternative method to assess adherence in both clinical research and practice.     

Motivational interviewing for improving adherence to antiretroviral medications

Many interventions have been developed to address barriers to antiretroviral medication adherence, but few have focused on motivation, a fundamental component of behavior change. Research on other health behavior changes and a few pilot studies investigating motivational interviewing (MI) for adherence to antiretroviral medication suggests that MI may be highly beneficial by helping to motivate patients with HIV to adhere to their medications. Existing research, although limited, suggests that MI combined with other interventions is feasible and efficacious for improving adherence to antiretroviral medications. With continued development and refinement of antiretroviral adherence interventions that incorporate MI, more persons with HIV infection can be expected to choose to make the difficult changes necessary for them to benefit from antiretroviral therapy.     

Clinical activity of leukotriene inhibitors

Data from the emerging clinical trials with compounds such as zileuton, ICI 204,219, Bay X1005, MK571, MK679, and MK591 are demonstrating the importance of the leukotrienes as mediators of asthma and possibly other diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. One of the major questions facing the asthma community is how much improvement in the FEV1 is needed to improve the quality of life of the asthmatic patient. Comparing the various approaches to asthma treatment, there is typically 15–20% improvement in the lung function with inhaled steroids. Leukotriene interventions apparently will improve lung function to similar levels as with inhaled steroids, and thus may offer an alternative to steroids. Like the steroids, zileuton appears to also reduce the inflammatory cell influx into the antigen-challenged site, which may have the long-term effect of reversing some of the tissue alterations that occur as a result of the inflammation seen with asthma. Importantly, the reported experience to date has shown that the leukotriene modulators do not have the same side-effects as the current therapies, and thus offer the hope that both safe and effective treatment may be derived from this approach. The clinical data reported do not yet define a preferred approach to the modulation of leukotriene pathology. As more studies are published in other diseases the broad spectrum use of these inhibitors will become known.     

Antiretroviral regimen complexity, self-reported adherence, and HIV patients' understanding of their regimens: survey of women in the her study

BACKGROUND: Research regarding treatment adherence in chronic diseases, such as hypertension, suggests that increasing complexity in the medication regimen is associated with decreasing patient adherence. However, less is known about the relationship between regimen complexity and adherence in the treatment of HIV/AIDS. OBJECTIVE: To examine the relationship between antiretroviral (ART) regimen complexity and patient understanding of correct regimen dosing to adherence (missing doses in the past 1 and 3 days). METHODS: Cross-sectional survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV Epidemiologic Research) Study. RESULTS: Seventy-five percent of patients correctly understood the dosing frequency of their ART medications, 80% understood the food-dosing restrictions, whereas only 63% understood both. The percentage of patients with a correct understanding of dosing decreased with increasing regimen complexity (increased dosing frequency and food-dosing restrictions). Patients were more likely to have missed doses in the previous 3 days if they were taking ART medications three or more times per day or had to take one or more antiretrovirals on an empty stomach. A multivariate logistic regression model demonstrated that patients with less complex regimens (twice daily or less in frequency, no food-dosing restrictions) who correctly understood the dosing and food restrictions of their ART regimen were less likely to have skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and higher CD4 count were also associated with a reduced likelihood of skipping doses. No association was found between adherence and race/ethnicity, current or past injection drug use, or education. CONCLUSIONS: Self-reported adherence is better among patients with less complex ART regimens. This is in part because patients' understanding of regimen dosing decreases as regimen complexity increases. Therefore, simplifying antiretroviral regimens may have an important role in improving patients' adherence.     

Mapping the categories of the Swedish primary health care version of ICD-10 to SNOMED CT concepts: Rule development and intercoder reliability in a mapping trial

Background

Decision aids (DA) are tools designed to help patients make specific and deliberative choices among disease management options. DAs can improve the quality of decision-making and reduce decisional conflict. An area not covered by a DA is the decision of a patient with chronic obstructive pulmonary disease (COPD) to use inhaled steroids which requires balancing the benefits and downsides of therapy.

Methods

We developed a DA for COPD patients considering inhaled steroid therapy using the Ottawa Decision Support Framework, the best available evidence for using inhaled steroid in COPD and the expected utility model. The development process involved patients, pulmonologists, DA developers and decision making experts. We pilot tested the DA with 8 COPD patients who completed an evaluation questionnaire, a knowledge scale, and a validated decisional conflict scale.

Results

The DA is a computer-based interactive tool incorporating four different decision making models. In the first part, the DA provides information about COPD as a disease, the different treatment options, and the benefits and downsides of using inhaled steroids. In the second part, it coaches the patient in the decision making process through clarifying values and preferences. Patients evaluated 10 out of 13 items of the DA positively and showed significant improvement on both the knowledge scale (p = 0.008) and the decisional conflict scale (p = 0.008).

Conclusion

We have developed a computer-based interactive DA for COPD patients considering inhaled steroids serving as a model for other DAs in COPD, in particular related to inhaled therapies. Future research should assess the DA effectiveness.     

Adherence to pharmacological treatment and specific immunotherapy in allergic rhinitis

The term compliance simply indicates how much doses of the prescribed medication are taken, whereas the term adherence implies also an agreement between patient and physician about the therapeutic plan, and it is therefore preferred. Adherence is a main problem in all long‐term treatments. Thus, it represents a problem also in the case of rhinitis, expecially concerning specific immunotherapy that must be assumed continuously for several years. Many factors can affect the adherence, depending on patient, on treatment itself and on the healthcare context, and all those factors usually interact. The adherence measured in controlled trials is usually good, but this does not reflect what happens in real life, where adherence should be preferably measured. There are few data on the adherence in real life for pharmacological treatments of allergic rhinitis (e.g. nasal steroids or antihistamines), whereas more data are available for specific immunotherapy. In this latter case, in real life, adherence seems to be far from optimal, for both sublingual and subcutaneous immunotherapy, although the recent studies agree on the fact that some interventions (i.e. patients’ education, strict follow‐up, regular contacts) could effectively improve the adherence. In this article, the literature concerning the adherence to pharmacological treatments and immunotherapy in allergic rhinitis was searched and reviewed.     

Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth

BACKGROUND: Inhaled steroids are recommended for the treatment of persistent asthma during pregnancy, but their potential effects on intrauterine growth have been inadequately evaluated. OBJECTIVE: The purpose of this study was to evaluate the association between maternal use of specific inhaled steroids and inhaled steroid dose during pregnancy and the incidence of infants who are small for gestational age (SGA) and mean birth weight. METHODS: Pregnant asthmatic women being treated with inhaled steroids were enrolled in the study before delivery by their managing allergists. Information regarding the specific inhaled steroid and daily dose used, requirement for oral steroids, occurrence of acute asthmatic episodes, maternal race, birth weight, gestational age, and congenital malformations was obtained for each patient. SGA was defined through use of a published normative sample of American births. RESULTS: A total of 474 women were enrolled in the study; of the 451 enrolled participants whose pregnancy ended in a singleton live birth, 396 (88%) completed the study. The incidence of infants with low birth weight, preterm births, and congenital malformations in this cohort was not greater than expected in the general population. The incidence of SGA was 7.1% (95% CI, 5.0% to 10.1%). No significant relationships between specific inhaled steroid or dose of inhaled steroid used and either SGA or mean birth weight were observed. CONCLUSION: These data suggest that the use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth and supports the recommendation that inhaled steroids should be used in the management of persistent asthma during pregnancy.