Bloqueantes del sistema Renina-Angiotensina e infección por COVID-19 / Renin-Angiotensin System Blockers And Covid-19 Infection

No disponible

Multimorbidity gender patterns in hospitalized elderly patients.

Patients with multimorbidity and complex health care needs are usually vulnerable elders with several concomitant advanced chronic diseases. Our research aim was to evaluate differences in patterns of multimorbidity by gender in this population and their possible prognostic implications, measured as in-hospital mortality, 1-month readmissions, and 1-year mortality. We focused on a cohort of elderly patients with well-established multimorbidity criteria admitted to a specific unit for chronic complex-care patients. Multimorbidity criteria, the Charlson, PROFUND and Barthel indexes, and the Pfeiffer test were collected prospectively during their stays. A total of 843 patients (49.2% men) were included, with a median age of 84 [interquartile range (IQR) 79-89] years. The women were older, with greater functional dependence [Barthel index: 40 (IQR:10-65) vs. 60 (IQR: 25-90)], showed more cognitive deterioration [Pfeiffer test: 5 (IQR:1-9) vs. 1 (0-6)], and had worse scores on the PROFUND index [15 (IQR:9-18) vs. 11.5 (IQR: 6-15)], all p <0.0001, while men had greater comorbidity measured with the Charlson index [5 (IQR: 3-7) vs. 4 (IQR: 3-6); p = 0.002]. In the multimorbidity criteria scale, heart failure, autoimmune diseases, dementia, and osteoarticular diseases were more frequent in women, while ischemic heart disease, chronic respiratory diseases, and neoplasms predominated in men. In the analysis of grouped patterns, neurological and osteoarticular diseases were more frequent in females, while respiratory and cancer predominated in males. We did not find gender differences for in-hospital mortality, 1-month readmissions, or 1-year mortality. In the multivariate analysis age, the Charlson, Barthel and PROFUND indexes, along with previous admissions, were independent predictors of 1-year mortality, while gender was non-significant. The Charlson and PROFUND indexes predicted mortality during follow-up more accurately in men than in women (AUC 0.70 vs. 0.57 and 0.74 vs. 0.62, respectively), with both p<0.001. In conclusion, our study shows differing patterns of multimorbidity by gender, with greater functional impairment in women and more comorbidity in men, although without differences in the prognosis. Moreover, some of these prognostic indicators had differing accuracy for the genders in predicting mortality.

Utility of FEV1/FEV6 index in patients with multimorbidity hospitalized for decompensation of chronic diseases.

Spirometry remains essential for the diagnosis of airway obstruction. Nevertheless, its performance in elderly hospitalized patients with multimorbidity can be difficult. The aim of this study is to assess the utility of the COPD-6 portable device in this population. We included all patients hospitalized for exacerbation of chronic diseases in a medical ward specialized in the care of multimorbidity patients, between September 2017 and May 2018. A questionnaire including sociodemographic, cognitive and functional impairment, among other variables, was completed the last day of admission. Subsequently, patients attempted to perform three valid respiratory manoeuvres with the COPD-6 device and then conventional spirometry. A total of 184 patients were included (mean age of 79.61 years, 55% men). Forty-seven (25.54%) patients were able to perform complete spirometric manoeuvres and 99 (53.8%) could perform a valid FEV1/FEV6 determination. The inability to perform a valid spirometry was related with the patient's age, functional physical disability, cognitive impairment or the presence of delirium or dysphagia during admission. Only 9% of patients with a Mini Mental Cognitive Examination (MMEC) lower than 24 points could perform a valid spirometry. Of the patients with an MMEC < 24 points and unable to perform spirometry, 34% were able to complete the FEV1/FEV6 manoeuvres. No differences were found in the Charlson index, multimorbidity scale, number of domiciliary drugs, or length of stay between those patients able and those not able to perform respiratory manoeuvres. The agreement between the values for FEV1 measured with COPD-6 and those observed in the spirometry was good (r: 0.71; p<0.0001). Inability to perform a valid spirometry during hospitalization in elderly patients with multimorbidity is frequent and related with functional and cognitive impairment. FEV1/FEV6 determination using the COPD-6 portable device allows an important percentage of the patients with limitations to complete spirometric measurement.

The Healthy Hearts and Kidneys (HHK) study: Design of a 2×2 RCT of technology-supported self-monitoring and social cognitive theory-based counseling to engage overweight people with diabetes and chronic kidney disease in multiple lifestyle changes.

Patients with complex chronic diseases usually must make multiple lifestyle changes to limit and manage their conditions. Numerous studies have shown that education alone is insufficient for engaging people in lifestyle behavior change, and that theory-based behavioral approaches also are necessary. However, even the most motivated individual may have difficulty with making lifestyle changes because of the information complexity associated with multiple behavior changes. The goal of the current Healthy Hearts and Kidneys study was to evaluate, different mobile health (mHealth)-delivered intervention approaches for engaging individuals with type 2 diabetes (T2D) and concurrent chronic kidney disease (CKD) in behavior changes. Participants were randomized to 1 of 4 groups, receiving: (1) a behavioral counseling, (2) technology-based self-monitoring to reduce information complexity, (3) combined behavioral counseling and technology-based self-monitoring, or (4) baseline advice. We will determine the impact of randomization assignment on weight loss success and 24-hour urinary excretion of sodium and phosphorus. With this report we describe the study design, methods, and approaches used to assure information security for this ongoing clinical trial. Clinical Trials.gov Identifier: NCT02276742.

Association Between High and Very High Albuminuria and Nighttime Blood Pressure: Influence of Diabetes and Chronic Kidney Disease.

OBJECTIVE: Nighttime blood pressure (BP) and albuminuria are two important and independent predictors of cardiovascular morbidity and mortality. Here, we examined the quantitative differences in nighttime systolic BP (SBP) across albuminuria levels in patients with and without diabetes and chronic kidney disease. RESEARCH DESIGN AND METHODS: A total of 16,546 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry cohort (mean age 59.6 years, 54.9% men) were analyzed. Patients were classified according to estimated glomerular filtration rate (eGFR), as ≥60 or <60 mL/min/1.73 m(2) (low eGFR), and urine albumin-to-creatinine ratio, as normoalbuminuria (<30 mg/g), high albuminuria (30-300 mg/g), or very high albuminuria (>300 mg/g). Office and 24-h BP were determined with standardized methods and conditions. RESULTS: High albuminuria was associated with a statistically significant and clinically substantial higher nighttime SBP (6.8 mmHg higher than with normoalbuminuria, P < 0.001). This association was particularly striking at very high albuminuria among patients with diabetes and low eGFR (16.5 mmHg, P < 0.001). Generalized linear models showed that after full adjustment for demographic, lifestyles, and clinical characteristics, nighttime SBP was 4.8 mmHg higher in patients with high albuminuria than in those with normoalbuminuria (P < 0.001), and patients with very high albuminuria had a 6.1 mmHg greater nighttime SBP than those with high albuminuria (P < 0.001). These differences were 3.8 and 3.1 mmHg, respectively, among patients without diabetes, and 6.5 and 8 mmHg among patients with diabetes (P < 0.001). CONCLUSIONS: Albuminuria in hypertensive patients is accompanied by quantitatively striking higher nighttime SBP, particularly in those with diabetes with very high albuminuria and low eGFR.

Prevalence, Treatment, and Control of Hypercholesterolemia in High Cardiovascular Risk Patients: Evidences from a Systematic Literature Review in Spain.

INTRODUCTION: Cardiovascular diseases (CVDs) represent a major Public Health burden. High serum cholesterol levels have been linked to major CV risk. The objectives of this study were to review the epidemiology of hypercholesterolemia in high risk CV patients from Spain, by assessing its prevalence, the proportion of diagnosed patients undergoing pharmacological treatment and the degree of attained lipid control. METHODS: A systematic literature review was carried out using Medline and two Spanish databases. Manuscripts containing information on hypercholesterolemia in several high CV risk groups [diabetes mellitus (DM), Systematic COronary Risk Evaluation (SCORE) risk >5, or documented CVD], published between January 2010 and October 2014, were included. RESULTS: Of the 1947 published references initially retrieved, a full-text review was done on 264 manuscripts and 120 were finally included. Prevalence of hypercholesterolemia ranged from 50 to 84% in diabetics, 30-60% in patients with DM or elevated SCORE risk, 64-74% with coronary heart disease, 40-70% in stroke patients, and 60-80% in those with peripheral artery disease. Despite the finding that most of them were on pharmacological treatment, acceptable control of serum lipids was very variable, ranging from 15% to 65%. Among those with heterozygous familial hypercholesterolemia, 95-100% received treatment but less than 50% achieved their therapeutic goals. CONCLUSIONS: An elevated prevalence of hypercholesterolemia can be found in targeted groups at high CV risk. Although most patients are receiving pharmacological treatment, rates of lipid control continue to be low, both in primary and secondary prevention.

Underdiagnosis and prognosis of chronic obstructive pulmonary disease after percutaneous coronary intervention: a prospective study.

BACKGROUND: Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI). The impact of undiagnosed COPD in these patients is unknown. We aimed to evaluate the prognostic impact of COPD - previously or newly diagnosed - in patients with IHD treated with PCI. METHODS: Patients with IHD confirmed by PCI were consecutively included. After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors. All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed. RESULTS: A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed. IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction. Median follow-up was 934 days (interquartile range [25%-75%]: 546-1,160). COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76-44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04-3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12-2.83). These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08-3.1). CONCLUSION: Prevalence and underdiagnosis of COPD in patients with IHD who undergo PCI are both high. These patients have an independent greater mortality and a higher number of cardiovascular events during follow-up.

Producción de bloques de agarosa para visualización de hongos / Agarose block preparation for fungi visualization

Establecer un protocolo para la obtención de bloques de hongos utilizando agarosa como matriz. Métodos: los hongos se incluyeron en agarosa, el proceso se estandarizó y se probaron los protocolos en horno microondas, convencional y en el procesador automático para la obtención de láminas siguiendo la técnica histológica usual. Conclusiones: el protocolo del procesador para obtener múltiples láminas es reproducible y las preparaciones permitieron la visualización fácil de los hongos con coloraciones de H&E y Gomori...

To establish a protocol to obtain fungi blocks in an agarose matrix. Methods: fungi were embedded in agarose, the process was standardized and protocols were tested using a microwave oven, a conventional oven and an automated processor to obtain slides following the usual histological technique. Conclusions: the multiple slides processor protocol is reproducible and preparations allowed easy visualization of fungi with H&E and Gomori stains. Key words: agarose cell block technique, fungi, hematoxylin and eosin, Gomori...

Control de la presión arterial en las mujeres hipertensas de 65 o más años de edad asistidas en atención primaria. Estudio MERICAP / Blood pressure control in hypertensive women aged 65 years or older in a primary care setting. MERICAP study

Introducción y objetivos. Es necesario tener más información sobre el grado de control de la hipertensión arterial en las mujeres. El objetivo de este estudio es analizar el control de presión arterial y los factores asociados al mal control en hipertensas asistidas en atención primaria. Métodos. Estudio transversal y multicéntrico que incluyó a mujeres de edad ≥ 65 años con diagnóstico establecido de hipertensión arterial. La medición de la presión arterial se realizó siguiendo normas estandarizadas, calculando la media aritmética de dos tomas sucesivas. Se consideró que había buen control cuando el promedio era < 140/90mmHg en general y < 130/80mmHg en pacientes con diabetes mellitus. Resultados. Se incluyó a 4.274 hipertensas; media de edad, 73,6±6,1 años. El 29,8% (intervalo de confianza del 95%, 28,4-31,1%) presentaba buen control de presión arterial sistólica y diastólica. El 67,6% estaba en terapia combinada (el 46,3 dos fármacos y el 21,7% tres o más). La lesión de órgano diana más frecuente fue la hipertrofia ventricular izquierda (33,8%) y la enfermedad clínica asociada más prevalente, la insuficiencia cardiaca (19%). Se observaron diferencias significativas según control de la presión arterial en todos los factores de riesgo cardiovascular, lesión órgano diana y enfermedad clínica asociada (p<0,01). La menor antigüedad de la hipertensión arterial, el colesterol unido a lipoproteínas de baja densidad > 115mg/dl, la glucohemoglobina ≥ 7%, la monoterapia y la obesidad fueron las variables que más se asociaron con mal control (p<0,0001). Conclusiones. Sólo 3 de cada 10 hipertensas de edad ≥ 65 años tenían controlada óptimamente su hipertensión arterial. El mal control se relacionó principalmente con un diagnóstico de hipertensión arterial más reciente (AU)

Introduction and objectives. The available information regarding blood pressure control in women is scarce. This study was aimed at assessing blood pressure control and predictors of a lack of blood pressure control in the primary care setting in a large sample of hypertensive women. Methods. Women aged 65 years or older with an established diagnosis of hypertension (≥6 months of evolution) were included in a cross-sectional, multicenter study. Blood pressure readings were taken following the current guidelines, and the value for each visit was the average of two separate measurements. Adequate blood pressure control was defined as <140/90mmHg (<130/80mmHg for diabetics). Results. A total of 4274 hypertensive women (mean age: 73.6 years [6.1 years]) were included in the study; blood pressure was controlled in 29.8% (95% confidence interval: 28.4%-31.1%) of the study population. Combined therapy was administered in 67.6% of patients (46.3% with 2 drugs and 21.7% with 3 or more drugs). The most common organ damage was left ventricular hypertrophy (33.8%) and the most common associated condition was heart failure (19%). Poor blood pressure control was more frequent in patients with more cardiovascular risk factors, organ damage, and associated clinical conditions (P<.01). A more recent hypertension diagnosis, LDL-cholesterol >115mg/dl, monotherapy, obesity, and hemoglobin A1c ≥7% were associated with a lack of blood pressure control (P<.0001). Conclusions. Only 3 in 10 hypertensive women aged ≥65 years monitored daily in the primary care setting achieved their blood pressure goals. A recent diagnosis of hypertension was the main predictor of poor blood pressure control (AU)

Blood pressure control in hypertensive women aged 65 years or older in a primary care setting. MERICAP study.

INTRODUCTION AND OBJECTIVES: The available information regarding blood pressure control in women is scarce. This study was aimed at assessing blood pressure control and predictors of a lack of blood pressure control in the primary care setting in a large sample of hypertensive women. METHODS: Women aged 65 years or older with an established diagnosis of hypertension (≥ 6 months of evolution) were included in a cross-sectional, multicenter study. Blood pressure readings were taken following the current guidelines, and the value for each visit was the average of two separate measurements. Adequate blood pressure control was defined as < 140/90 mm Hg (< 130/80 mm Hg for diabetics). RESULTS: A total of 4274 hypertensive women (mean age: 73.6 years [6.1 years]) were included in the study; blood pressure was controlled in 29.8% (95% confidence interval: 28.4%-31.1%) of the study population. Combined therapy was administered in 67.6% of patients (46.3% with 2 drugs and 21.7% with 3 or more drugs). The most common organ damage was left ventricular hypertrophy (33.8%) and the most common associated condition was heart failure (19%). Poor blood pressure control was more frequent in patients with more cardiovascular risk factors, organ damage, and associated clinical conditions (P<.01). A more recent hypertension diagnosis, LDL-cholesterol > 115 mg/dl, monotherapy, obesity, and hemoglobin A(1c) ≥ 7% were associated with a lack of blood pressure control (P < .0001). CONCLUSIONS: Only 3 in 10 hypertensive women aged ≥ 65 years monitored daily in the primary care setting achieved their blood pressure goals. A recent diagnosis of hypertension was the main predictor of poor blood pressure control.

Detection of unrecognized clinical heart failure in elderly hypertensive women attended in primary care setting.

OBJECTIVE: To determine the proportion and clinical features of unrecognized heart failure (HF) in hypertensive women ≥65 years attended in Spain. METHODS: A cross-sectional study carried out in primary healthcare setting. Patients were considered to present unrecognized clinical diagnosis of HF if they had not been previously diagnosed but fulfilled Framingham criteria for HF diagnosis. RESULTS: Of 3500 patients, the proportion of unrecognized clinical HF was 26.3%. In comparison with women without HF, all cardiovascular risk factors were more prevalent in patients with unrecognized HF; the same was observed for target organ damage, being the most frequent left ventricular hypertrophy (LVH) (54.1% vs 15.5%, p<0.0001), and for the presence of cardiovascular disease, being the most common coronary heart disease (24.8% vs 9.8%, p<0.0001). Predictive factors associated with the presence of unrecognized HF were LVH (OR =4.84) and the presence of previous cardiovascular disease (OR =2.26) Blood pressure control was worse in patients with unrecognized HF (16.6% vs 33.9%, p <0.01). CONCLUSIONS: More than a quarter of hypertensive women ≥65 years may have clinical data of unrecognized HF. Hypertensive women with unrecognized clinical HF have a worse clinical profile and worse BP control rates than those without HF.

Respuesta al autor: Excesos clínicos de la conferencia de consenso sobre hipertensión arterial / Author's reply: Clinical overdoing of consensus conference about hypertension

No disponible

No disponible

Discrepancies between office and ambulatory blood pressure: clinical implications.

BACKGROUND: Recent trials have documented no benefit from small reductions in blood pressure measured in the clinical office. However, ambulatory blood pressure is a better predictor of cardiovascular events than office-based blood pressure. We assessed control of ambulatory blood pressure in treated hypertensive patients at high cardiovascular risk. METHODS: We selected 4729 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Patients were aged >/=55 years and presented with at least one of the following co-morbidities: coronary heart disease, stroke, and diabetes with end-organ damage. An average of 2 measures of blood pressure in the office was used for analyses. Also, 24-hour ambulatory blood pressure was recorded at 20-minute intervals with a SpaceLabs 90207 device. RESULTS: Patients had a mean age of 69.6 (+/-8.2) years, and 60.8% of them were male. Average time from the diagnosis of hypertension to recruitment into the Registry was 10.9 (+/-8.4) years. Mean blood pressure in the office was 152.3/82.3 mm Hg, and mean 24-hour ambulatory blood pressure was 133.3/72.4 mm Hg. About 60% of patients with an office-pressure of 130-139/85-89 mm Hg, 42.4% with office-pressure of 140-159/90-99 mm Hg, and 23.3% with office-pressure > or =160/100 mm Hg were actually normotensive, according to 24-hour ambulatory blood pressure criteria (<130/80 mm Hg). CONCLUSION: We suggest that the lack of benefit of antihypertensive therapy in some trials may partly be due to some patients having normal pressure at trial baseline. Ambulatory monitoring of blood pressure may allow for a better assessment of trial eligibility.

Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer.

PURPOSE: Aromatase inhibitors (AIs) improve survival in postmenopausal women with hormone-sensitive breast cancer, but can cause joint pain and stiffness. The purpose of the current study was to evaluate the prevalence of and identify risk factors for AI-related joint symptoms. PATIENTS AND METHODS: We performed a cross-sectional survey of consecutive postmenopausal women receiving adjuvant AI therapy for early-stage hormone-sensitive breast cancer at an urban academic breast oncology clinic. Patients completed a 25-item self-administered questionnaire assessing the presence of joint symptoms that started or worsened after initiating AIs. Multivariate regression was used to compare those with AI-related arthralgia with those who did not report symptoms, adjusting for demographic and clinical factors. RESULTS: Of 200 patients who completed the survey, 94 (47%) reported having AI-related joint pain and 88 (44%) reported AI-related joint stiffness. In multiple logistic regression analysis, being overweight (body mass index of 25 to 30 kg/m(2)) and prior tamoxifen therapy were inversely associated with AI-related joint symptoms. Patients who received taxane chemotherapy were more than four times more likely than other patients to have AI-related joint pain and stiffness (odds ratio [OR] = 4.08, 95% CI, 1.58 to 10.57 and OR = 4.76; 95% CI, 1.84 to 12.28, respectively). CONCLUSION: Our study suggests that AI-related joint symptoms are more prevalent than what has been described previously in clinical trials. The success of AI therapy depends on patients' ability to adhere to treatment recommendations; therefore, additional studies of interventions that may alleviate these symptoms are needed.

Ambulatory blood pressure monitoring in hypertensive patients with high cardiovascular risk: a cross-sectional analysis of a 20,000-patient database in Spain.

OBJECTIVE: To evaluate ambulatory blood pressure monitoring (ABPM) parameters in a broad sample of high-risk hypertensive patients. METHODS: The Spanish Society of Hypertension is developing a nationwide project in which more than 900 physicians send ABPM registries and corresponding clinical records to a central database via www.cardiorisc.com. Between June 2004 and July 2005 a 20 000-patient database was obtained; 17 219 were valid for analysis. RESULTS: We identified 6534 patients with high cardiovascular risk according to the 2003 European Society of Hypertension/European Society of Cardiology guidelines stratification score. Office blood pressure (BP) was 158.8/89.9 mmHg and 24-h BP was 135.8/77.0 mmHg. Patients with grade 3 BP in the office showed ambulatory systolic BP values less than 160 mmHg in more than 80%. A non-dipping pattern was observed in 3836 cases (58.7%), whereas this abnormality was present in 47.9% of patients with low-to-moderate risk [odds ratio (OR) 1.54; 95% confidence interval (CI) 1.45-1.64]. The prevalence of non-dippers was higher as ambulatory BP increased ( approximately 70% when 24-h systolic BP > 155 mmHg) and was similar in both groups. At the lowest levels of BP (24-h systolic BP < 135 mmHg) a non-dipping pattern was more prevalent in high-risk cases (56.6 versus 45.7%; OR 1.51; 95% CI 1.40-1.64). CONCLUSION: There was a remarkable discrepancy between office and ambulatory BP in high-risk hypertensive patients. The prevalence of a non-dipper BP pattern was almost 60%. In the lowest levels of ambulatory BP, high-risk patients showed a higher prevalence of non-dipping BP than lower-risk cases. These observations support the recommendation of a wider use of ABPM in high-risk hypertensive patients.

Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.

INTRODUCTION: Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias. METHODS: Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha. RESULTS: Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported. DISCUSSION/CONCLUSIONS: In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated. IMPLICATIONS FOR CANCER SURVIVORS: Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.