Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials.

Objective: We aimed to perform a meta-analysis evaluating the efficacy and safety of dupilumab in patients with uncontrolled asthma. Data source: A search of electronic databases was performed using PubMed, Cochrane library and Embase. Study selection: The literature search was conducted independently by two reviewers. Only randomized controlled trials (RCTs) that compared between placebo and dupilumab in patients with uncontrolled asthma were included in this analysis. Pooled risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were calculated for dichotomous and continuous data, respectively. Results: A total of four RCTs representing 2,992 patients were included. Pooled analysis showed significant reductions of the annualized rate of severe asthma exacerbation in the dupilumab group compared with placebo (RR 0.44; 95% CI 0.35-0.055; P < 0.01; I2 = 42%). In addition, the absolute forced expiratory volume at 1 s (FEV1) changes were significantly increased for the dupilumab group (MD 0.14; 95% CI: 0.12-0.17; P < 0.01; I2 = 0%). Finally, there were no significant differences between both groups in the development of any adverse event, serious adverse events, adverse events leading to death, discontinuation of medication due to adverse event or the occurrence of upper respiratory tract, influenza or bronchitis infections. However, dupilumab was associated with an increased risk of injection site reactions compared with placebo (RR 1.91; 95% CI 1.41, 2.59; P < 0.01; I2 = 24%). Conclusion: Among patients with uncontrolled asthma, the addition of dupilumab was associated with a reduced risk of severe asthma exacerbations and improvement in FEV1 without an increased risk of adverse events apart from injection site reactions with dupilumab.

Long-acting Muscarinic Antagonist Versus Inhaled Corticosteroid when Added to Long-acting ß-agonist for COPD: A Meta-analysis.

The purpose of this study was to systematically review the efficacy and safety of long-acting ß-agonist/long-acting muscarinic antagonist (LABA/LAMA) and LABA/inhaled corticosteroid (ICS) combinations in patients with advanced chronic obstructive pulmonary disease (COPD). Randomized clinical trials of at least 12 weeks of duration comparing LABA/LAMA and LABA/ICS combinations were included. We chose forced expiratory volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score, Transitional Dyspnea Index (TDI), COPD Assessment Test (CAT) score, COPD exacerbations, mortality, and other safety parameters as outcome assessment criteria. We included six randomized controlled trials with a total of 4,319 patients. Most patients did not have a history of exacerbation. LABA/LAMA was associated with greater improvement in FEV1 than LABA/ICS (mean difference (MD) 0.09L, 95%confidence interval (CI) 0.07 to 0.11L; high certainty). Two treatments appeared clinically equivalent in improving SGRQ (MD -0.12, 95%CI -1.16 to 0.92; high certainty), TDI (MD 0.15, 95%CI -0.05 to 0.35; high certainty), and CAT scores (MD 0.28 95%CI -0.29 to 0.85; moderate certainty). LABA/LAMA was associated with an absolute reduction of approximately 8% in the incidence of pneumonia compared with LABA/ICS (risk ratio 0.41, 95%CI 0.18 to 0.94; moderate certainty). There was no significant difference in safety and exacerbation outcomes. However, equivalence of two treatments could not be concluded due to imprecision especially for mortality, cardiac serious adverse events, and severe exacerbations. Our findings support the use of dual long-acting bronchodilators for patients with advanced COPD but without frequent exacerbations given the excess risk of pneumonia with LABA/ICS.

Mycobacterium chimaera lung infection and empyema in a patient without cardiopulmonary bypass.

Mycobacterium chimaera is a nontuberculous mycobacterium that belongs to the Mycobacterium avium complex. Invasive infections are very rare and have been associated with contaminated heater-cooler water systems used during cardiopulmonary bypass. There is usually a long latency period and patients have nonspecific symptoms that can result in a delayed diagnosis or misdiagnosis. We report a case of M. chimaera infection in a man who presented with worsening shortness of breath and was found to have pleural effusion. The patient did not have any history of cardiopulmonary bypass surgery, which raises concerns about community spread of this rare infection and needs further investigation in the general population. Furthermore, he had a history of sarcoidosis and was on immunosuppressive medications, which might suggest that immunosuppressed patients can acquire this infection without the described risk factors.

The Impact of Diabetes Mellitus in Patients with Chronic Obstructive Pulmonary Disease (COPD) Hospitalization.

(1) Background: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. Diabetes mellitus (DM) has been shown to have adverse inflammatory effects on lung anatomy and physiology. We investigated the impact of DM on COPD patient outcomes during inpatient hospitalization. (2) Methods: We conducted a retrospective analysis using the Nationwide Inpatient Sample (NIS) over the years 2002-2014. Three groups, COPD without diabetes, COPD with diabetes but no complication, and COPD with DM and complication, were analyzed. (3) Results: A total of 7,498,577 were COPD hospitalization; of those, 1,799,637 had DM without complications, and 483,467 had DM with complications. After adjusting for clinical, demographic, and comorbidities, the odds of increased LOS in the COPD/DM with complication were 1.37 (confidence interval (CI): 1.326-1.368), and those of DM without complication were 1.061 (1.052-1.070) when compared with COPD alone. The odds of pneumonia, respiratory failure, stroke, and acute kidney injury were also higher in COPD hospitalizations with DM. Both DM with complication (odds ratio (OR): 0.751 (CI 0.727-0.777)) and DM without complication (OR: 0.635 (CI: 0.596-0.675)) have lesser odds of mortality during hospitalization than with COPD alone. (4) Conclusions: There is a considerable inpatient burden among COPD patients with DM in the United States.

A 29-Year-Old Male with a Fatal Case of COVID-19 Acute Respiratory Distress Syndrome (CARDS) and Ventilator-Induced Lung Injury (VILI).

BACKGROUND COVID-19 patients that develop acute respiratory distress syndrome (ARDS) "CARDS" behave differently compared to patients with classic forms of ARDS. Recently 2 CARDS phenotypes have been described, Type L and Type H. Most patients stabilize at the milder form, Type L, while an unknown subset progress to Type H, resembling full-blown ARDS. If uncorrected, phenotypic conversion can induce a rapid downward spiral towards progressive lung injury, vasoplegia, and pulmonary shrinkage, risking ventilator-induced lung injury (VILI) known as the "VILI vortex". No cases of in-hospital phenotypic conversion have been reported, while ventilation strategies in these patients differ from the lung-protective approaches seen in classic ARDS. CASE REPORT A 29-year old male was admitted with COVID-19 pneumonia complicated by severe ARDS, multi-organ failure, cytokine release syndrome, and coagulopathy during his admission. He initially resembled CARDS Type L case, although refractory hypoxemia, fevers, and a high viral burden prompted conversion to Type H within 8 days. Despite ventilation strategies, neuromuscular blockade, inhalation therapy, and vitamin C, he remained asynchronous to the ventilator with volumes and pressures beyond accepted thresholds, eventually developing a fatal tension pneumothorax. CONCLUSIONS Patients that convert to Type H can quickly enter a spiral of hypoxemia, shunting, and dead-space ventilation towards full-blown ARDS. Understanding its nuances is vital to interrupting phenotypic conversion and entry into VILI vortex. Tension pneumothorax represents a poor outcome in patients with CARDS. Further research into monitoring lung dynamics, modifying ventilation strategies, and understanding response to various modes of ventilation in CARDS are required to mitigate these adverse outcomes.

A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants.

Anticoagulation carries a tremendous therapeutic advantage in reducing morbidity and mortality with venous thromboembolism and atrial fibrillation. For over six decades, traditional anticoagulants like low molecular weight heparin and vitamin K antagonists like warfarin have been used to achieve therapeutic anticoagulation. In the past decade, multiple new direct oral anticoagulants have emerged and been approved for clinical use. Since their introduction, direct oral anticoagulants have changed the landscape of anticoagulants. With increasing indications and use in various patients, they have become the mainstay of treatment in venous thromboembolic diseases. The safety profile of direct oral anticoagulants is better or at least similar to warfarin, but several recent reports are focusing on spontaneous hemorrhages with direct oral anticoagulants. This narrative review aims to summarize the incidence of spontaneous hemorrhage in patients treated with direct oral anticoagulants and also offers practical management strategies for clinicians when patients receiving direct oral anticoagulants present with bleeding complications.

Impact of a Positive Viral Polymerase Chain Reaction on Outcomes of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.

INTRODUCTION: More than 15 million adults in the USA have chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) places a high burden on the healthcare system. Many hospital admissions are due to an exacerbation, which is suspected to be from a viral cause. The purpose of this analysis was to compare the outcomes of patients with a positive and negative respiratory virus panel who were admitted to the hospital with COPD exacerbations. METHODS: This retrospective cohort study was conducted in the Geisinger Healthcare System. The dataset included 2729 patient encounters between 1 January 2006 and 30 November 2017. Hospital length of stay was calculated as the discrete number of calendar days a patient was in the hospital. Patient encounters with a positive and negative respiratory virus panel were compared using Pearson's chi-square or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon rank-sum tests for continuous variables. RESULTS: There were 1626 patients with a total of 2729 chronic obstructive pulmonary disease exacerbation encounters. Nineteen percent of those encounters (n = 524) had a respiratory virus panel performed during their admission. Among these encounters, 161 (30.7%) had positive results, and 363 (69.3%) had negative results. For encounters with the respiratory virus panel, the mean age was 64.5, 59.5% were female, 98.9% were white, and the mean body mass index was 26.6. Those with a negative respiratory virus panel had a higher median white blood cell count (11.1 vs. 9.9, p = 0.0076). There were no other statistically significant differences in characteristics between the two groups. Respiratory virus panel positive patients had a statistically significant longer hospital length of stay. There were no significant differences with respect to being on mechanical ventilation or ventilation-free days. CONCLUSION: This study shows that a positive respiratory virus panel is associated with increased length of hospital stay. Early diagnosis of chronic obstructive pulmonary disease exacerbation patients with positive viral panel would help identify patients with a longer length of stay.

Triple versus dual inhaler therapy in moderate-to-severe COPD: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. OBJECTIVES: To perform a meta-analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled-glucocorticoid (ICS), long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) when compared with dual therapy (ICS-LABA or LAMA-LABA). METHODS: We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate-ratio (RR) or odds-ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). RESULTS: Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate-to-severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69-0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07-0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD -1.67; 95% CI -2.02- -1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19-1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03-1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. CONCLUSIONS: Among patients with moderate-to-severe COPD, triple inhaler therapy was associated with a reduction of moderate-to-severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

C1q Nephropathy: The Unique Underrecognized Pathological Entity.

C1q nephropathy is a rare glomerular disease with characteristic mesangial C1q deposition noted on immunofluorescence microscopy. It is histologically defined and poorly understood. Light microscopic features are heterogeneous and comprise minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and proliferative glomerulonephritis. Clinical presentation is also diverse, and ranges from asymptomatic hematuria or proteinuria to frank nephritic or nephrotic syndrome in both children and adults. Hypertension and renal insufficiency at the time of diagnosis are common findings. Optimal treatment is not clear and is usually guided by the underlying light microscopic lesion. Corticosteroids are the mainstay of treatment, with immunosuppressive agents reserved for steroid resistant cases. The presence of nephrotic syndrome and FSGS appear to predict adverse outcomes as opposed to favorable outcomes in those with MCD. Further research is needed to establish C1q nephropathy as a universally recognized distinct clinical entity. In this paper, we discuss the current understanding of pathogenesis, histopathology, clinical features, therapeutic options, and outcomes of C1q nephropathy.