A systematic review and meta-analysis of macrolides in the management of adult patients with asthma.

BACKGROUND: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma. METHODS: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides. RESULTS: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo. CONCLUSIONS: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.

Prospective Real-World Analysis of Asthma Patients With Preserved and Reduced Physical Activity.

BACKGROUND: Asthma is a highly heterogeneous airway disease, and the clinical characteristics of patients with asthma with preserved and reduced physical activity are poorly understood. OBJECTIVE: We aimed to investigate the risk factors and clinical phenotypes associated with reduced physical activity in a wide range of patients with asthma. METHODS: We conducted a prospective observational study of 138 patients with asthma, including patients with asthma without chronic obstructive pulmonary disease (COPD) (n = 104) and asthma-COPD overlap (n = 34), and 42 healthy controls. Physical activity levels were measured for 2 weeks using a triaxial accelerometer at baseline and 1 year later. RESULTS: Higher eosinophils and body mass index (BMI) were associated with reduced physical activity in patients with asthma without COPD. Cluster analysis of asthma without COPD revealed 4 asthma phenotypes. We identified a cluster with preserved physical activity (n = 43) that was characterized by good symptom control and lung function and included a high proportion of biologics users (34.9%). Multivariate regression analysis revealed that patients with late-onset eosinophilic (n = 21), high-BMI noneosinophilic (n = 14), and symptom-predominant asthma phenotypes (n = 26) had lower levels of physical activity than controls. Patients with asthma-COPD overlap also had significantly lower physical activity levels than controls. Similar trends in physical activity levels were observed in each asthma group at 1-year follow-up. CONCLUSION: This study showed the clinical features of patients with asthma with preserved and reduced physical activity. Reduced physical activity was observed in various asthma phenotypes and in asthma-COPD overlap.

Vocal cord dysfunction detected by a three-dimensional image of dynamic change in respiratory resistance in a patient with difficult-to-treat asthma: a case report.

INTRODUCTION: Vocal cord dysfunction (VCD) often coexists with asthma and exacerbates respiratory symptoms. A noninvasive method could be considered beneficial for the detection and follow-up of VCD complicated by asthma. Here, we report a case of VCD complicated by asthma, highlighting the effectiveness of colored three-dimensional (3-D) imaging of respiratory impedance using a broadband frequency forced oscillation technique (MostGraph). CASE STUDY: A 74-year-old woman with difficult-to-treat asthma, in whom mepolizumab treatment was ineffective, was referred to our hospital. Stridulous sounds were loudest over the anterior neck. Pulmonary function tests' results were normal; however, a flattening of the inspiratory flow-volume curve was detected. RESULTS: Remarkably, prominent spikes were observed in the inspiratory phase in the colored 3-D imaging of respiratory resistance, which was superimposed on increased respiratory resistance in the expiratory phase. Flexible laryngoscopy revealed the adduction of vocal cords on inspiration. The patient was diagnosed with asthma complicated by VCD. After successful treatment of VCD by speech therapy, inspiratory spikes of respiratory resistance disappeared, and normal vocal cord movement was observed on laryngoscopy. CONCLUSION: The present case report indicates the effectiveness of forced oscillometry in evaluating dynamic changes in respiratory resistance for detecting and monitoring VCD complicated by asthma.

Dupilumab as an adjunct treatment for a patient with steroid-dependent immunoglobulin G4-related disease complicated by asthma: a case report.

Introduction: Immunoglobulin G4-related disease (IgG4-RD) responds well to glucocorticoids but is often associated with relapses. Interleukin (IL)-4 and IL-13 are involved in the pathogenesis of IgG4-RD. We present the first case in which dupilumab was an effective adjunct treatment for a patient with steroid-dependent IgG4-RD complicated by asthma.Case study: A 57-year-old man was referred to our hospital for further investigation and treatment of proptosis with neck swelling in 2019. He developed a cough and swelling of the neck in 2016. He was diagnosed with asthma in 2017 and started receiving inhaled glucocorticoids and a long-acting beta-agonist. The patient started receiving oral prednisolone at a dose of 20 mg/day. Oral prednisolone reduced his symptoms, but he relapsed when treatment was tapered to less than 10 mg/day. He was diagnosed with IgG4-RD through a parotid gland biopsy.Results: Azathioprine was given to reduce systemic glucocorticoids. The prednisolone dose was gradually tapered to 10 mg/day, resulting in the relapse of proptosis and an asthma attack. We added dupilumab, and his asthma symptoms and proptosis improved. Serum IgG4 levels continued to decrease, and the prednisolone dose was tapered to 2 mg.Conclusion: Dupilumab might be useful as an adjunctive treatment for patients with steroid-dependent IgG4-RD complicated by asthma. Serum IgG4 levels can be used as a marker to monitor dupilumab treatment in IgG4-RD.

Association between glucose intolerance and chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease.

PURPOSE: Cytotoxic chemotherapy-induced lung injury is a fatal complication in patients with lung cancer and interstitial lung disease (ILD). We aimed to evaluate the association between hyperglycemia and this form of lung injury in patients with lung cancer concomitant with ILD. METHODS: From 1147 patients with advanced lung cancer, we retrospectively enrolled 98 patients with ILD whose hemoglobin A1c (HbA1c) levels were measured, and investigated the association between HbA1c levels and cytotoxic chemotherapy-induced lung injury. In 73 patients whose serum samples were retained, we measured serum levels of advanced glycation end products (AGE) and assessed the association of AGE levels with HbA1c levels and cytotoxic chemotherapy-induced lung injury. RESULTS: The incidence of cytotoxic chemotherapy-induced lung injury was significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8%, but not in those with HbA1c levels ≥ 6.5% than in those with HbA1c levels < 6.5%. The multivariate logistic regression model revealed that HbA1c level ≥ 5.8% was a significant risk factor for this complication [odds ratio 3.178 (95% confidence interval 1.057-9.556), P = 0.040]. In addition, serum AGE levels were significantly higher in patients with HbA1c levels ≥ 5.8% than in those with HbA1c levels < 5.8% [median (interquartile range); 0.129 (0.023-0.290) and 0.474 (0.213-1.109) µg/mL, P = 0.001]. CONCLUSION: Glucose intolerance (e.g., HbA1c level ≥ 5.8%) may be a risk factor of cytotoxic chemotherapy-induced lung injury, which might be associated with elevated AGE production due to hyperglycemia.

Risk factors associated with increased discontinuation rate of trimethoprim-sulfamethoxazole used as a primary prophylaxis for Pneumocystis pneumonia: A retrospective cohort study.

BACKGROUND: The use of trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis pneumonia (PcP) prophylaxis is often discontinued owing to adverse drug reactions. Half-dosage of TMP-SMX (40/200 mg daily) is considered more tolerable than the conventional dosage (80/400 mg daily). However, patient background characteristics that are associated with the discontinuation of TMP-SMX prophylaxis and suitable for reduced dosage remain unclear. In this study, we aimed to identify the risk factors for the discontinuation of and efficacy of different doses of TMP-SMX prophylaxis in patients with creatinine clearance higher than 30 mL/min. METHODS: We retrospectively evaluated 318 immunocompromised non-human immunodeficiency virus (HIV)-infected patients (194 men and 124 women; median age, 68.5 [interquartile range, 59-75] years) who underwent TMP-SMX therapy as a primary PcP prophylaxis between July 2014 and August 2019. The patients were segregated into two groups on the basis of dosage: single-strength (SS; n = 244) and half-strength (HS; n = 74) groups. We evaluated PcP occurrence, TMP-SMX discontinuation rate, and discontinuation-related risk factors in these groups. RESULTS: PcP did not occur in either group. The univariate and multivariate Cox proportional hazards models revealed that the SS dosage and renal function (e.g. serum creatinine and creatinine clearance) were independently associated with prophylaxis discontinuation. At 24 weeks, the HS group presented significantly lower discontinuation rates than the SS group (P = 0.019, log-rank test). In the SS group, patients with mild renal impairment (e.g. serum creatinine ≥0.78 mg/dL or creatinine clearance ≤64.26 mL/min) presented significantly higher TMP-SMX discontinuation rates than those without such an impairment (P < 0.05, log-rank test with Bonferroni correction). This difference was not significant in the HS group. CONCLUSION: Mild renal impairment might increase the risk of discontinuation of conventional TMP-SMX prophylaxis. In patients with a mild renal impairment, the HS dosage may improve tolerability while maintaining prophylactic efficacy.

[A Case of Lung Cancer Associated with Drug-Induced Immune Thrombocytopenia].

A Stage IV lung adenocarcinoma was diagnosed in the left upper lobe of an 81-year-old man 2.5 years ago. Following another form of chemotherapy, he then received docetaxel as fourth-line therapy. After 21 days of therapy, although his white blood cell count recovered, his platelet count decreased to 20,000/mL and continued to decrease. Subsequently, he was closely monitored without therapy, and eventually, his platelet count returned within the normal range after 112 days. Blood biochemistry and bone marrow paracentesis findings suggested the presence of paraneoplastic syndrome, idiopathic thrombocytopenic purpura, and drug-induced immune thrombocytopenia. It was difficult to distinguish between the presence of myelosuppression, carcinoma with bone marrow invasion, and paraneoplastic syndrome. This is believed to have resulted from a docetaxel-induced immune thrombocytopenia because, although the platelet count decreased after docetaxel chemotherapy, it eventually returned to normal levels without therapy.