37 research outputs found

    Bronchial Thermoplasty Induced Airway Smooth Muscle Reduction and Clinical Response in Severe Asthma:The TASMA Randomized Trial

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    RATIONALE: Bronchial Thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT but appropriate control groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT treatment is important. AIMS: First, to assess the effect of BT on ASM mass and second, to identify patient characteristics that correlate with BT-response. METHODS: Severe asthma patients (n=40) were randomized to immediate (n=20) or delayed (n=20) BT-treatment. Prior to randomization, clinical, functional, blood and airway biopsy data were collected. In the delayed control group, re-assessment, including biopsies, was performed after 6 months of standard clinical care, followed by BT. In both groups, post-BT data including biopsies were obtained after 6 months. ASM mass (% positive desmin or α-smooth muscle actin area in the total biopsy) was calculated with automated digital analyses software. Associations between baseline characteristics and Asthma Control and Asthma Quality of Life Questionnaire (ACQ/AQLQ) improvement were explored. RESULTS: Median ASM mass decreased by >50% in the immediate BT group (n=17) versus no change in the delayed control group (n=19) (p=0.0004). In the immediate group ACQ scores improved with -0.79 (-1.61;0.02 IQR) compared to 0.09 (-0.25;1.17 IQR) in the delayed group (p=0.006). AQLQ scores improved with 0.83 (-0.15;1.69 IQR) versus -0.02 (-0.77;0.75 IQR) (p=0.04). Treatment response in the total group (n=35) was positively associated with serum IgE and eosinophils, but not with baseline ASM mass. CONCLUSION: ASM mass significantly decreases after BT when compared to a randomized non-BT treated control group. Treatment response was associated with serum IgE and eosinophil levels but not with ASM mass. Clinical trial registration available at www.clinicaltrials.gov, ID:NCT0222539

    Long-Term Weight Changes After Starting Anti-IL-5/5Ra Biologics in Severe Asthma: The Role of Oral Corticosteroids

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    BACKGROUND Many patients with severe asthma are overweight or obese, often attributed to unintentional weight gain as a side effect of oral corticosteroids (OCSs). Anti-IL-5/5Ra biologics significantly reduce OCS use, but their long-term effects on weight are unknown. OBJECTIVES To examine (1) weight change up to 2 years after anti-IL-5/5Ra initiation in subgroups on the basis of maintenance OCS use at start of treatment and (2) whether cumulative OCS exposure before or changes in OCS exposure during treatment are related to weight change. METHODS Real-world data on weight and cumulative OCS dose from adults included in the Dutch Registry of Adult Patients with Severe asthma for Optimal DIsease management before and at least 2 years after starting anti-IL-5/5Ra were analyzed using linear mixed models and linear regression analyses. RESULTS For the included 389 patients (55% female; mean body mass index, 28 ± 5 kg/m2^{2}; 58% maintenance OCS), mean weight decreased -0.27 kg/y (95% CI, -0.51 to -0.03; P = .03), with more weight loss in patients with maintenance OCS use than in those without maintenance OCS use (-0.87 kg/y [95% CI, -1.21 to -0.52; P < .001] vs +0.54 kg/y [0.26 to 0.82; P < .001]). Greater weight loss at 2 years was associated with higher cumulative OCS dose in the 2 years before anti-IL-5/5Ra initiation (ÎČ = -0.24 kg/g; 95% CI, -0.38 to -0.10; P < .001) and, independently, greater reduction in cumulative OCS dose during follow-up (ÎČ = 0.27 kg/g; 95% CI, 0.11 to 0.43; P < .001). CONCLUSIONS Anti-IL-5/5Ra therapy is associated with long-term weight reduction, especially in patients with higher OCS exposure before treatment and those able to reduce OCS use during treatment. However, the effect is small and does not apply to all patients, and so additional interventions seem necessary if weight change is desired

    Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression

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    RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 ”M forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences

    Alpine altitude climate treatment for severe and uncontrolled asthma: an EAACI position paper

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    Currently available European Alpine Altitude Climate Treatment (AACT) programs combine the physical characteristics of altitude with the avoidance of environmental triggers in the alpine climate and a personalized multidisciplinary pulmonary rehabilitation approach. The reduced barometric pressure, oxygen pressure, and air density, the relatively low temperature and humidity, and the increased UV radiation at moderate altitude induce several physiological and immunological adaptation responses. The environmental characteristics of the alpine climate include reduced aeroallergens such as house dust mites (HDM), pollen, fungi, and less air pollution. These combined factors seem to have immunomodulatory effects controlling pathogenic inflammatory responses and favoring less neuro-immune stress in patients with different asthma phenotypes. The extensive multidisciplinary treatment program may further contribute to the observed clinical improvement by AACT in asthma control and quality of life, fewer exacerbations and hospitalizations, reduced need for oral corticosteroids (OCS), improved lung function, decreased airway hyperresponsiveness (AHR), improved exercise tolerance, and improved sinonasal outcomes. Based on observational studies and expert opinion, AACT represents a valuable therapy for those patients irrespective of their asthma phenotype, who cannot achieve optimal control of their complex condition despite all the advances in medical science and treatment according to guidelines, and therefore run the risk of falling into a downward spiral of loss of physical and mental health. In the light of the observed rapid decrease in inflammation and immunomodulatory effects, AACT can be considered as a natural treatment that targets biological pathways

    Ernstig astma bij volwassenen

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    The Dutch guideline 'Diagnostics and treatment of severe asthma' provides recommendations on the diagnosis and treatment of patients older than 18 years with severe asthma. A checklist was developed to determine which diagnostic trajectory should be implemented in patients with 'difficult to treat asthma' before the diagnosis of 'severe asthma' can be made. Evidence-based recommendations are made in accordance with the GRADE method, with regard to additional treatment on top of the standard treatment of high dosages of inhaled corticosteroids combined with long-acting beta2 agonists. Furthermore, recommendations are made on the monitoring and follow-up of patients with severe asthma and on the setting up of specialized centres for patients suffering from severe asthma. This guideline is primarily meant for pulmonologists. However, it may also be useful for other disciplines involved in the care for patients with asthm

    Tobramycin and vestibulotoxicity: Retrospective analysis of four cases

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    Over a course of 7 months, four patients developed vestibulotoxicity after treatment with intravenous tobramycin. Since vestibulotoxicity is a serious adverse effect which can be irreversible, an investigation was undertaken to determine if there was a cause for the toxicity and whether the quality of care had been inadequate. In this period, 26 patients with cystic fibrosis were treated with tobramycin according to valid guidelines, of which four experienced acute dizziness which disrupted their daily activities. Two patients experienced irreversible bilateral vestibular hypofunction and two unilateral loss of the right labyrinth, with decreasing dizziness over time. No apparent cause for the vestibulotoxicity was found in these four patients and the simultaneous occurrence was not due to a lack in quality of care. Symptoms of dizziness and balance disorders should be recognised by patients and caretakers at an early stage so additional diagnostics can be done to prevent further deterioration

    Predictors for the development of progressive severity in new-onset adult asthma

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    A proportion of patients with adult-onset asthma have severe disease. Risk factors for an increase in asthma severity are poorly known. We sought to identify predictors for the development of severe asthma in adults. A cohort of 200 adults with new-onset asthma was prospectively followed for 2 years. At baseline, patients underwent a comprehensive assessment of clinical, functional, and inflammatory parameters. After 2 years, change in asthma severity was assessed by using the Global Initiative for Asthma score (range, 1-4), which is based on asthma control (Asthma Control Questionnaire), lung function (FEV1), and inhaled corticosteroid requirement. ANOVA and multiple regression equations were used in the analysis. One hundred twenty-eight patients completed 2 years of follow-up. Seventeen (13.3%) patients had an increase in asthma severity, whereas 53 (41.4%) patients had a decrease. A lower postbronchodilator FEV1/forced vital capacity ratio and a higher number of cigarette pack years smoked at baseline were significantly associated with an increase in asthma severity at follow-up. Multiple regression equations showed that only the number of cigarette pack years smoked was independently associated with an increase in asthma severity, with an odds ratio of 1.4 (95% CI, 1.02-1.91) for every 10 pack years smoked. A history of cigarette smoking in patients with new-onset adult asthma predicts an increase in asthma severity during the first 2 years of the disease in a dose-dependent manne

    A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia

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    Hypertonic saline inhalation lowers airway mucous viscosity. Increased cough transportability may improve quality of life (QoL) in primary ciliary dyskinesia (PCD).In this randomised controlled trial (RCT), PCD patients received twice-daily inhalations of hypertonic (7%) saline or isotonic (0.9%) saline for 12 weeks, with 4 weeks washout during crossover. Primary outcome was change in QoL measured by the St George's Respiratory Questionnaire (SGRQ) total score. Secondary outcomes were SGRQ subscores, Quality of Life Questionnaire-Bronchiectasis (QoL-B) scores, lower respiratory tract infection symptoms, exacerbations, spirometry, systemic and sputum inflammatory markers, adherence, and adverse events.There was no significant change in median (interquartile range) SGRQ total score between hypertonic saline (-2.6 (-9.0-1.5)) and isotonic saline (-0.3 (-8.1-6.1)) in 22 patients (age range 22-73 years) (p=0.38). QoL-B Health Perception scale improved with hypertonic saline (p=0.03). Adverse events occurred more frequently with hypertonic saline, but were mild.12 weeks of inhaled hypertonic saline did not improve SGRQ total score in adult PCD patients in this RCT, but the sample size was small. On the secondary and more disease-specific end-point of the QoL-B, a significant improvement was observed in the Health Perception scale. This study found little evidence to support the hypothesis that hypertonic saline improves QoL in PCD patients. We advise the use of disease-specific outcome measures in future trial

    Permanent cortical blindness after bronchial artery embolization

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    A 35-year-old female with a known medical history of cystic fibrosis was admitted to our institution for massive hemoptysis. CTA depicted a hypertrophied bronchial artery to the right upper lobe and showed signs of recent bleeding at that location. Bronchial artery embolization (BAE) was performed with gelfoam slurry, because pronounced shunting to the pulmonary artery was present. Immediately after BAE, the patient developed bilateral cortical blindness. Control angiography showed an initially not opacified anastomosis between the embolized bronchial artery and the right subclavian artery, near to the origin of the right vertebral artery. Cessation of outflow in the bronchial circulation reversed the flow through the anastomosis and allowed for spill of embolization material into the posterior circulation. Unfortunately the cortical blindness presented was permanen
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