Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Asthma self-assessment in a Medicaid population

<p>Abstract</p> <p>Background</p> <p>Self-assessment of symptoms by patients with chronic conditions is an important element of disease management. A recent study in a commercially-insured population found that patients who received automated telephone calls for asthma self-assessment felt they benefitted from the calls. Few studies have evaluated the effectiveness of disease self-assessment in Medicaid populations. The goals of this study were to: (1) assess the feasibility of asthma self-assessment in a population predominantly insured by Medicaid, (2) study whether adding a gift card incentive increased completion of the self-assessment survey, and (3) evaluate how the self-assessment affected processes and outcomes of care.</p> <p>Methods</p> <p>We studied adults and children aged 4 years and older who were insured by a Medicaid-focused managed care organization (MCO) in a pre- and post-intervention study. During the pre-incentive period, patients with computerized utilization data that met specific criteria for problematic asthma control were mailed the Asthma Control Test (ACT), a self-assessment survey, and asked to return it to the MCO. During the intervention period, patients were offered a $20 gift card for returning the completed ACT to the MCO. To evaluate clinical outcomes, we used computerized claims data to assess the number of hospitalization visits and emergency department visits experienced in the 3 months after receiving the ACT. To evaluate whether the self-management intervention improved processes of care, we conducted telephone interviews with patients who returned or did not return the ACT by mail.</p> <p>Results</p> <p>During the pre-incentive period, 1183 patients were identified as having problems with asthma control; 25 (2.0%) of these returned the ACT to the MCO. In contrast, during the incentive period, 1612 patients were identified as having problems with asthma control and 87 (5.4%) of these returned the ACT to the MCO (p < 0.0001). Of all 95 ACTs that were returned, 87% had a score of 19 or less, which suggested poor asthma control.</p> <p>During the 3 months after they received the ACT, patients who completed it had similar numbers of outpatient visits, emergency department visits, and hospitalizations for asthma as patients who did not complete the ACT. We completed interviews with 95 patients, including 28 who had completed the ACT and 67 who had not. Based on an ACT administered at the time of the interview, patients who had previously returned the ACT to the MCO had asthma control similar to those who had not (mean scores of 14.2 vs. 14.6, p = 0.70). Patients had similar rates of contacting their providers within the past 2 months whether they had completed the mailed ACT or not (71% vs. 76%, p = 0.57).</p> <p>Conclusion</p> <p>Mailing asthma self-assessment surveys to patients with poorly controlled asthma was not associated with better asthma-associated outcomes or processes of care in the Medicaid population studied. Adding a gift card incentive did not meaningfully increase response rates. Asthma disease management programs for Medicaid populations will most likely need to involve alternative strategies for engaging patients and their providers in managing their conditions.</p

Comparison of physical fitness between healthy and mild‐to‐moderate asthmatic children with exercise symptoms: A cross‐sectional study

.Objective Asthma is a chronic disease that may affect physical fitness, although its primary effects on exercise capacity, muscle strength, functionality and lifestyle, in children and adolescents, are still poorly understood. This study aimed to evaluate the differences in cardiorespiratory fitness, muscle strength, lifestyle, lung function, and functionality between asthmatics with exercise symptoms and healthy children. In addition, we have analyzed the association between clinical history and the presence of asthma. Study Design Cross-sectional study including 71 patients with a diagnosis of asthma and 71 healthy children and adolescents (7–17 years of age). Anthropometric data, clinical history, disease control, lifestyle (KIDMED and physical activity questionnaires), lung function (spirometry), exercise-induced bronchoconstriction test, aerobic fitness (cardiopulmonary exercise test), muscle strength and functionality (timed up and go; timed up and down stairs) were evaluated. Results Seventy-one patients with asthma (mean age 11.5 ± 2.7) and 71 healthy subjects (mean age 10.7 ± 2.5) were included. All asthmatic children had mild to moderate and stable asthma. EIB occurred in 56.3% of asthmatic children. Lung function was significantly (p < .05) lower in the asthmatic group when compared to healthy peers, as well as the cardiorespiratory fitness, muscle strength, lifestyle and functionality. Moreover, asthmatic children were more likely to have atopic dermatitis, allergic reactions, food allergies, and a family history of asthma when compared to healthy children. Conclusions Children with mild-to-moderate asthma presenting exercise symptoms show a reduction in cardiorespiratory fitness, muscle strength, lung function, functionality, and lifestyle when compared to healthy peers. The study provides data for pediatricians to support exercise practice aiming to improve prognosis and quality of life in asthmatic children.S

Study protocol for Women of Color and Asthma Control: A randomized controlled trial of an asthma-management intervention for African American women

<p>Abstract</p> <p>Background</p> <p>Among adults in the United States, asthma prevalence is disproportionately high among African American women; this group also experiences the highest levels of asthma-linked mortality and asthma-related health care utilization. Factors linked to biological sex (e.g., hormonal fluctuations), gender roles (e.g., exposure to certain triggers) and race (e.g., inadequate access to care) all contribute to the excess asthma burden in this group, and also shape the context within which African American women manage their condition. No prior interventions for improving asthma self-management have specifically targeted this vulnerable group of asthma patients. The current study aims to evaluate the efficacy of a culturally- and gender-relevant asthma-management intervention among African American women.</p> <p>Methods/Design</p> <p>A randomized controlled trial will be used to compare a five-session asthma-management intervention with usual care. This intervention is delivered over the telephone by a trained health educator. Intervention content is informed by the principles of self-regulation for disease management, and all program activities and materials are designed to be responsive to the specific needs of African American women. We will recruit 420 female participants who self-identify as African American, and who have seen a clinician for persistent asthma in the last year. Half of these will receive the intervention. The primary outcomes, upon which the target sample size is based, are number of asthma-related emergency department visits and overnight hospitalizations in the last 12 months. We will also assess the effect of the intervention on asthma symptoms and asthma-related quality of life. Data will be collected via telephone survey and medical record review at baseline, and 12 and 24 months from baseline.</p> <p>Discussion</p> <p>We seek to decrease asthma-related health care utilization and improve asthma-related quality of life in African American women with asthma, by offering them a culturally- and gender-relevant program to enhance asthma management. The results of this study will provide important information about the feasibility and value of this program in helping to address persistent racial and gender disparities in asthma outcomes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01117805">NCT01117805</a></p

Decreased TNF-α synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging

Immunity declines during aging, however the mechanisms involved in this decline are not known. In this study, we show that cutaneous delayed type hypersensitivity (DTH) responses to recall antigens are significantly decreased in older individuals. However, this is not related to CC chemokine receptor 4, cutaneous lymphocyte-associated antigen, or CD11a expression by CD4+ T cells or their physical capacity for migration. Instead, there is defective activation of dermal blood vessels in older subject that results from decreased TNF-α secretion by macrophages. This prevents memory T cell entry into the skin after antigen challenge. However, isolated cutaneous macrophages from these subjects can be induced to secrete TNF-α after stimulation with Toll-like receptor (TLR) 1/2 or TLR 4 ligands in vitro, indicating that the defect is reversible. The decreased conditioning of tissue microenvironments by macrophage-derived cytokines may therefore lead to defective immunosurveillance by memory T cells. This may be a predisposing factor for the development of malignancy and infection in the skin during aging

Airway smooth muscle as a target of asthma therapy: history and new directions

Ultimately, asthma is a disease characterized by constriction of airway smooth muscle (ASM). The earliest approach to the treatment of asthma comprised the use of xanthines and anti-cholinergics with the later introduction of anti-histamines and anti-leukotrienes. Agents directed at ion channels on the smooth muscle membrane (Ca(2+ )channel blockers, K(+ )channel openers) have been tried and found to be ineffective. Functional antagonists, which modulate intracellular signalling pathways within the smooth muscle (β-agonists and phosphodiesterase inhibitors), have been used for decades with success, but are not universally effective and patients continue to suffer with exacerbations of asthma using these drugs. During the past several decades, research energies have been directed into developing therapies to treat airway inflammation, but there have been no substantial advances in asthma therapies targeting the ASM. In this manuscript, excitation-contraction coupling in ASM is addressed, highlighting the current treatment of asthma while proposing several new directions that may prove helpful in the management of this disease

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.