Muscle Function in Moderate to Severe Asthma:Association With Clinical Outcomes and Inflammatory Markers

BackgroundPatients with severe asthma have been shown to have low muscle mass, but the clinical consequences are unknown.ObjectiveIn a clinical cohort of patients with moderate to severe asthma, we aimed to assess muscle mass and strength and their relation with functional and clinical outcomes, as well as with systemic inflammatory markers.MethodsMuscle mass and strength were assessed by the fat-free mass index (FFMI), creatinine excretion in a 24-hour urine sample, and handgrip strength test. Functional outcomes included pulmonary function tests and the 6-minute walking distance, whereas clinical outcomes were assessed with questionnaires on asthma control, quality of life, and health care use. Associations of muscle mass and strength with asthma outcomes were assessed with multivariable regression analyses.ResultsA total of 114 patients participated (36% male; mean age, 51.9 ± 14.4 years; body mass index, 27.7 ± 5.7 kg/m2). According to predefined criteria, 16% had a low FFMI and 8% a low urinary creatinine excretion, which did not differ between categories of asthma severity. Both lower FFMI and urinary creatinine excretion were associated with lower values of FEV1 and 6-minute walking distance, whereas a lower handgrip strength was related to worse asthma control, poorer quality of life, and a higher probability of emergency visits (all P < .05). Except for higher leukocytes in relation to lower FFMI, we did not find associations between systemic inflammatory markers and muscle function.ConclusionsThis study demonstrates that low muscle mass is prevalent in patients with moderate to severe asthma and, along with low muscle strength, is associated with poorer clinical and functional outcomes. Our results encourage longitudinal studies into muscle function as a potential target for treatment to improve asthma outcomes

Dietary Inflammatory Index and clinical outcome measures in adults with moderate to severe asthma

BACKGROUND: Diet is increasingly recognized as a modifiable factor in lung health, predominantly due to the immunomodulatory effects of nutrients. The Dietary Inflammatory Index (DII) is a score developed to express the inflammatory potential of a diet.OBJECTIVE: We aimed to assess the association of the DII and food groups, with clinical, functional and inflammatory asthma outcomes in adults with asthma.METHODS: Patients with moderate to severe asthma were included in this cross-sectional study between June 2019 and October 2021, and completed a 3-day food diary, to calculate the DII and intake of food groups (i.e. fruits, whole grains, processed meats and sugar-sweetened beverages). Functional outcomes included pulmonary function tests and the 6-minute walking distance, while clinical outcomes were assessed using questionnaires on asthma control, quality of life, and healthcare utilization. Inflammatory markers were exhaled nitric oxide and blood leukocytes, eosinophils and interleukin-6. Multivariable regression analyses were used to examine the association of DII and food groups with asthma outcomes.RESULTS: A total of 109 patients participated (35% male, mean±SD age 51.8 ± 14.2 years, BMI 27.4 ± 5.3 kg/m 2). Overall, 62% had a DII score &gt;0, indicating a pro-inflammatory diet, which was not related to asthma severity. A more pro-inflammatory diet was consistently associated to lower FVC (%pred), but inconsistent results were observed with respect to airway obstruction. Neither the DII nor food groups were associated with clinical outcomes. Except for higher levels of exhaled nitric oxide in relation to an anti-inflammatory diet, we found no associations between inflammatory markers and the DII. CONCLUSION: Results from this cross-sectional study among patients with moderate to severe asthma do not support the hypothesis that a pro-inflammatory diet is associated with worse asthma outcomes, although limitations in study design and dietary intake estimation should be considered. Future well-designed experimental studies are needed to assess whether targeting the inflammatory potential of diet could lead to better outcomes in adults with asthma.</p

Administration of benralizumab in a patient with severe asthma admitted to the intensive care unit with COVID-19 pneumonia:Case report

A patient with severe asthma on benralizumab therapy was admitted to the intensive care unit (ICU) for a coronavirus disease 2019 (COVID-19) infection. At the end of the 8 week benralizumab dosing interval, discussion arose as to whether benralizumab should be administered or if treatment should be discontinued, due to the lack of experience with benralizumab in this situation. Severe broncho-obstruction developed, and the next injection of benralizumab was administered during ICU admission without detrimental symptoms. With this case report, we would like to share our experience with the safe administration of benralizumab during COVID-19 pneumonia, guiding doctors in future decision making

Diet quality, food intake and incident adult-onset asthma:a Lifelines Cohort Study

PURPOSE: Dietary factors have been suggested as drivers of the rising prevalence of adult-onset asthma, but evidence is inconclusive, possibly due to the complex interrelation with obesity. We aim to explore the relation of diet quality and food intake with incident adult-onset asthma in normal weight and overweight adults of the prospective population-based Lifelines Cohort Study.METHODS: Incident adult-onset asthma was defined as self-reported asthma at ± 4-year follow-up, in adults free of airway disease at baseline. Diet quality scores and food group intake were assessed at baseline. Log-binomial regression analyses were used to estimate adjusted relative risks (RR) between dietary intake (per portion) and incident adult-onset asthma, in categories of BMI (cutoff: 25 kg/m 2). RESULTS: 477 incident asthma cases (75% female, 62% overweight) and 34,698 controls (60% female, 53% overweight) were identified. Diet quality-assessed by the Lifelines Diet Score and Mediterranean Diet Score-was not associated with incident adult-onset asthma in the two BMI groups. Although the dietary intake of several food groups differed between cases and controls, after adjustment for confounders only few remained associated with adult-onset asthma, including red and processed meat (RR: 0.93 per 15 g intake; 95% CI 0.86-0.99) in the normal weight group and intake of cheese (RR 1.09 per 20 g intake; 95% CI 1.00-1.17) and vegetables (RR 1.10 per 50 g intake; 95% CI 1.00-1.21) in the overweight group.CONCLUSION: The results of this study question the role of food as a 'simple' predictor of adult-onset asthma and call for an integrative approach, including a range of modifiable lifestyle factors and further asthma phenotyping.</p

Patient-reported outcome measures after 8 weeks of mepolizumab treatment and long-term outcomes in patients with severe asthma:an observational study

Background The novel anti-IL-5 drug mepolizumab improves asthma outcomes in the majority but not all patients with severe eosinophilic asthma. Currently it is difficult to predict an individuals' chance of being a responder. Early changes in patient-reported outcome measures may contribute to the prediction of long-term outcomes. Aim To compare early changes in patient-reported outcome measures after 8 weeks and long-term response to mepolizumab treatment. Method 22 severe eosinophilic asthma patients starting mepolizumab therapy in a severe asthma centre in the Netherlands were evaluated on baseline, 8 weeks and 52 weeks, collecting questionnaire scores and asthma-related parameters. Well-controlled asthma was defined as an asthma control questionnaire score ≤ 0.75. Long-term treatment response was defined as continuing mepolizumab therapy at 52 weeks. Results Nine patients (41%) had well-controlled asthma at 8 weeks and all were mepolizumab responders at 52 weeks (positive predictive value = 100%, 95%CI 66-100), versus only 5 responders out of 13 patients with not well-controlled asthma at 8 weeks (negative predictive value = 62%, 95%CI 32-86). Conclusion The results in this study suggest that patients receiving mepolizumab therapy with an ACQ-score ≤ 0.75 at 8 weeks are unlikely to need extensive monitoring, for they are very likely to be long-term responders

Refractory&quot; eosinophilic airway inflammation in severe asthma: effect of parenteral corticosteroids

It has been suggested that patients with refractory eosinophilic airway inflammation represent a separate &quot;eosinophilic&quot; asthma phenotype associated with increased morbidity and a poor prognosis. To investigate whether persistent eosinophilia in these patients is a fixed feature or can still be modified by treatment, we investigated the effect of high-dose intramuscular corticosteroids on eosinophils in induced sputum. Twenty-two patients with stable severe asthma (15 women, aged 21-73 years) participated in this double-blind, placebo-controlled study. All were using inhaled corticosteroids (у 1,600 g/day) or chronic oral prednisone. They were included if the percentage of eosinophils in induced sputum was above the upper limit of normal (у 2%). Two weeks after treatment with triamcinolone, but not placebo, sputum eosinophils almost completely disappeared from a median of 12.6-0.2% (p Ͻ 0.001). In 82% of patients, no eosinophils could be observed at all. In addition, the rescue medication score decreased from 1.4 to 0.8 (p ϭ 0.01), and FEV 1 improved from a median of 73.8-88.3% predicted (p ϭ 0.001). We conclude that persistent sputum eosinophilia despite extensive antiasthma treatment is not a refractory phenomenon but is still sensitive to high-dose systemic corticosteroids. This implies that these patients with severe asthma need additional or alternative antiinflammatory treatment to combat the eosinophilia and associated poor prognosis. Keywords: asthma; eosinophilia; glucocorticoids; phenotype; sputum; severity of illness index There is now accumulating evidence that patients with bronchial asthma are heterogeneous with respect to the type of inflammation in the airways and the response to antiinflammatory therapy (1-4). Most patients with asthma have eosinophilic airway inflammation with good response to treatment with inhaled corticosteroids (5). However, a relatively large proportion of adult asthma cases is characterized by neutrophilic airway inflammation (4, 6), in particular those with severe disease (7-9). These patients are more difficult to treat and often require high doses of inhaled or oral corticosteroids to control their disease. Remarkably, bronchial biopsy and bronchoalveolar lavage studies have shown that in a subgroup of patients with severe asthma such neutrophilic airway inflammation is accompanied by persistent eosinophilic inflammation (10, 11). Eosinophilic inflammation in the airway mucosa that persists despite the use of high doses of inhaled corticosteroids or oral corticosteroids has been observed in several studies Correspondence and requests for reprints should be addressed to Elisabeth H. and has been implicated by Wenzel and colleagues as a feature of a separate asthma phenotype, associated with poor asthma prognosis (10, 12). Indeed, studies have shown that eosinophilic inflammation despite vigorous antiasthma treatment is associated with remodeling of the airways, impaired lung function, and near-fatal asthma attacks Why eosinophilia is persisting in these patients is unknown. Moreover, it has not been investigated whether persistent eosinophilia is a permanent characteristic of a specific phenotype of severe asthma or can be modulated by more intensive treatment. In this study, we investigated the effect of high-dose intramuscular corticosteroids on sputum eosinophilia in a subgroup of patients with severe asthma featuring persistent eosinophilia despite extensive antiinflammatory treatment. In addition, the effect of intramuscular corticosteroids on asthma symptoms, lung function, peripheral blood eosinophils, and nitric oxide in exhaled breath was examined. The results of this study have been published previously in the form of an abstract (21). METHODS Patients The patients in this study were part of a cohort of severe asthma patients participating in studies aimed at identifying risk factors of asthma severity Design The study had a randomized, parallel, double-blind, placebo-controlled design. At baseline (Visit 1), patients&apos; characteristics were documented, and Borg score, postbronchodilator FEV 1 , and level of exhaled nitric oxide were assessed. A blood sample was taken, and sputum was induced. If the sputum eosinophil percentage exceeded 2%, patients were randomized to one of the two treatments, with stratification for daily use of oral steroids (strata yes/no), and level of sputum eosinophil percentage (strata 2-10% or Ͼ 10%). After 1 week (Visit 2), one single intramuscular injection of 3 ml (40 mg/ml) long-acting triamcinolone acetonide (Kenacort-A40; Bristol-Myers Squibb, Woerden, The Netherlands) or matched placebo (3 ml NaCl 0.9%) was given. Intramuscular administration was chosen instead of a course of oral corticosteroids to avoid any confounding by noncompliance with therapy. Two weeks thereafter (Visit 3), the measurements performed at Visit 1 were repeated. A diary was completed by the patients during the first and third weeks of the study. Measurements Postbronchodilator FEV 1 was assessed (24) 30 minutes after the inhalation of 400 g salbutamol, and exhaled nitric oxide measurements wer

Effect of dietary interventions on markers of type 2 inflammation in asthma:A systematic review

INTRODUCTION: Type 2 (T2) inflammation is a key mechanism in the pathophysiology of asthma. Diet may have immunomodulatory effects, and a role for diet in T2 inflammation has been suggested in the literature. Indeed, diet and food allergies play a role in children with atopic asthma, but less is known about diet in relation to adult asthma, which is often non-atopic.OBJECTIVE: To review the effect of dietary interventions on markers of T2 inflammation in adults with asthma.METHODS: The databases PubMed, Embase, Cochrane Library, and CINAHL were searched for eligible studies until December 2022. We included studies of all types of foods, nutrients, diets or supplements, either as an exposure or as an intervention, in adults and adolescents with asthma. Outcomes of interest included the T2 biomarkers FeNO, eosinophils, IL-4, IL-5, IL-13, eosinophil cationic protein and eosinophil peroxidase. The methodological quality of eligible studies was systematically evaluated, and the results were summarised according to dietary clusters.RESULTS: The systematic search identified studies on the dietary clusters antioxidants (n = 14), fatty acids, (n = 14), Mediterranean-style diets (n = 5), phytotherapy (n = 7), prebiotics &amp; probiotics (n = 8), vitamin D (n = 7), and other dietary factors (n = 5). Studies within the phytotherapy and omega-3 poly-unsaturated fatty acids (PUFA) clusters showed possible improvements in T2 inflammation. Furthermore, we found little evidence for an effect of antioxidants, prebiotics &amp; probiotics, and Mediterranean-style diets on T2 inflammation. However, heterogeneity in study protocols, methodological shortcomings and limited power of almost all studies make it difficult to fully determine the impact of different dietary approaches on T2 inflammation in asthma.CONCLUSIONS: Overall, the current evidence does not support a specific dietary intervention to improve T2 inflammation in asthma. Interventions involving phytotherapy and omega-3 PUFA currently have the best evidence and warrant further evaluation in well-designed and adequately powered studies, while taking into account T2-high phenotypes of asthma.</p