Clinical Features and Treatment Outcomes of Pulmonary Mycobacterium avium-intracellulare Complex With and Without Coinfections.

Coinfections are more common in patients with cystic fibrosis and bronchiectasis. Infiltrates on imaging studies are seen more commonly in patients with coinfections, but coinfections did not affect treatment outcomes of pulmonary Mycobacterium avium complex.

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work, and improves their long-term lung function. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 7 March 2022. We also searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 3 May 2022. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the certainty of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Five trials with 183 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and three trials (106 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials but, for four out of five trials, we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis. One trial was a cross-over design and we only included data from the first intervention arm. Inhaled antibiotics alone versus intravenous antibiotics alone Only one trial (18 participants) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-certainty evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-certainty evidence). With regards to our secondary outcomes, one trial (18 participants) reported no difference in the need for additional antibiotics and the second trial (59 participants) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-certainty evidence). The single trial (18 participants) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-certainty  evidence). Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics alone Inhaled antibiotics plus intravenous antibiotics may make little or no difference to quality of life compared to intravenous antibiotics alone. None of the trials reported time off work or school. All three trials measured lung function, but found no difference between groups in forced expiratory volume in one second (two trials; 44 participants; very low-certainty evidence) or vital capacity (one trial; 62 participants). None of the trials reported on the need for additional antibiotics. Inhaled plus intravenous antibiotics may make little difference to the time to next exacerbation; however, one trial (28 participants) reported on hospital admissions and found no difference between groups. There is likely no difference between groups in adverse events (very low-certainty evidence) and one trial (62 participants) reported no difference in the emergence of antibiotic-resistant organisms (very low-certainty evidence). AUTHORS' CONCLUSIONS: We identified only low- or very low-certainty evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.

Effects of race on the outcome of COVID-19 in hospitalized patients.

BACKGROUND AND AIMS: Recent reports indicate that African Americans have higher mortality rates from SARS-CoV-2 coronavirus disease 19 (COVID-19) compared to Caucasians, with more marked differences in the Midwest region of the US. This study was performed to study differences in COVID-19 related mortality and hospital length of stay (LOS) between African Americans and Caucasians in Midwest setting, and identify factors associated with mortality and LOS. METHODS: Data were collected from the electronic health records (EHR) of patients admitted to hospitals in Midwest region of the US. EHR of 471 COVID-19 patients were reviewed. RESULTS: Approximately 63% were African Americans and 34% Caucasians. One hundred sixteen variables were tested. There was no significant difference in hospital mortality between African Americans and Caucasians (OR 1, 95% CI 0.48-1.94). Older age, Chronic kidney disease, mental status change, mechanical ventilation, vasopressor support, high neutrophil count, elevated AST and ALT, high lung involvement severity score and elevated CRP were associated with mortality in a univariate analysis (P < 0.05). Multivariable modeling indicated that mechanical ventilation was the only factor that predicted mortality (OR 6, 95% CI: 2.94-12.48). The LOS did not differ in African Americans and Caucasians. The use of oxygen via high flow nasal cannula (Survival Estimate 1.6, 95% CI: 1.20-2.26), low estimated glomerular filtration rate (Survival Estimate 1.4, 95% CI: 1.05-1.82) and mechanical ventilation (Survival Estimate 3.5, 95% CI: 2.72-4.37) were predictors of LOS. CONCLUSION: This study performed in Midwest setting in the US showed that race did not affect in-hospital mortality and LOS. Our analysis demonstrated new predictors of LOS.

Effectiveness of one-on-one coaching in improving pressurized metered dose inhaler (pMDI) technique among COPD patients: a prospective clinical study.

BACKGROUND: Incorrect use of inhalers among asthma and COPD patients is very prevalent. Yet, no single intervention is considered standard of care. We aimed to conduct a COPD-specific investigation of active one-on-one coaching as the educational intervention to improve pressurized metered dose inhaler (pMDI) technique and COPD symptoms management. METHODS: COPD patients who have pMDI in their treatment regimen were enrolled in this prospective study using the Global Initiative for Chronic Obstructive Lung Disease criteria. After rapid cognitive screen, inhaler technique was assessed and an active one-on-one coaching was provided utilizing the 12-step American Thoracic Society instructions. Patients' inhaler technique was assessed and scored again at their regular follow-up visits. RESULTS: One hundred and one patients participated in the study. The percentage of pMDI misuse decreased from 43.5% pre-teaching to 12.9% post-teaching (binomial test p value < 0.001). The mean number of errors decreased from 3.1 errors pre-teaching to 1.7 errors post-teaching (paired t-test p value < 0.001). The number needed to treat was 3.3 patients to prevent one misuse. Patients with an impaired cognitive function were more likely to have inhaler misuse in general and less likely to improve their technique when provided training. CONCLUSIONS: This study reveals that many COPD patients have incorrect pMDI techniques that can be improved with a short training in the clinic. TRIAL REGISTRATION: Not applicable.

Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease.

BACKGROUND: The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study was conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the United States. METHODS: We conducted a 10-year (2005-2015) retrospective study at 7 Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information was abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. RESULTS: Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio, 4.5, 95% confidence interval, 2.0-10.4; P < .001). Overall mortality was 15.7%. CONCLUSIONS: Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

Trends and seasonal variation of hospitalization and mortality of interstitial lung disease in the United States from 2006 to 2016.

BACKGROUND: In the recent years, the overall trends in hospital admission and mortality of interstitial lung disease (ILD) are unknown. In addition, there was some evidence that interstitial lung disease death rate highest in the winter but this finding was only available in one study. This study will investigate the trend and seasonal variations in hospital admission and mortality rates of ILD from 2006 to 2016. METHOD: From the Nationwide Inpatient Sample database, we collected all cases with the International Classification of Diseases (ICD)-9 or ICD-10 codes of ILD excluding identifiable external causes (drug, organic or inorganic dusts) from 2006 to 2016. Hospitalization rates of each year were calculated based on U.S Census population data. Monthly hospitalization and in-hospital mortality rates were analyzed by seasonal and trend decomposition. Subgroups of idiopathic interstitial fibrosis (IPF), acute respiratory failure (ARF), pneumonia were analyzed. RESULTS: From 2006 to 2016, all-cause hospital admission rate of patients with interstitial lung disease (ILD) and IPF-only subgroup declined but their overall mortality remained unchanged (except IPF subgroup and acute respiratory failure subgroup). Acute respiratory failure related admission account for 23% of all causes and pneumonia 17.6%. Mortality of ILD in general and subgroup of ILD with ARF was highest in winter, up to 8.13% ± 0.60 and 26.3% ± 10.2% respectively. The seasonal variations of hospital admission and mortality of ILD in general was not changed when infectious pneumonia cases were ruled out. All cause admission rates were highest in months from January to April. Subgroup analysis also showed seasonal variations with highest hospitalization rates for all subgroups (IPF, ARF, pneumonia) in the months from December to April (winter to early Spring). CONCLUSION: From 2006 to 2016, admission rates of ILD of all causes and IPF subgroup declined but in-hospital mortality of ILD of all causes remained unchanged. Mortality of IPF subgroup and acute respiratory failure subgroup trended down. All-cause hospital admissions and mortality of ILD have a strong seasonal variation. Hospitalization rates for all subgroups (IPF, ARF, pneumonia) were highest in the months from December to April.

Effect of Very Low-Dose Hydrocortisone on Shock Reversal in Patients With Septic Shock.

In patients with septic shock, hydrocortisone 200-400 mg/d has been shown to reverse shock compared with placebo. Lower doses of hydrocortisone have not previously been studied, and there are no previous studies comparing two different doses of hydrocortisone. At our institution, some clinicians routinely prescribe doses less than 200 mg/d. This study aims to compare the effect of lower doses of hydrocortisone to standard doses on shock reversal and adverse events in septic shock. DESIGN: Retrospective cohort study. SETTING: Single-center medical ICU. SUBJECTS: Patients who received hydrocortisone for septic shock. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Patients were divided into low-dose hydrocortisone (75-150 mg/d) and standard-dose hydrocortisone (200-400 mg/d) cohorts based on initial prescribed hydrocortisone dose. Rates of shock reversal and adverse events in the two cohorts were compared. Two-hundred thirteen patients were included-41 in low-dose and 172 in standard-dose cohorts. Baseline characteristics including initial vasopressor requirement and Sequential Organ Failure Assessment scores were similar. Average rates of change in vasopressor needs, conditional hazard rate for vasopressor withdrawal, and cumulative probability for vasopressor withdrawal were all quantitatively similar for low-dose and standard-dose hydrocortisone. Insulin requirement (particularly in those with diabetes mellitus), blood glucose in those with diabetes mellitus, and frequency of secondary infections seemed to be lower in the low-dose hydrocortisone cohort. Mortality and other secondary outcomes were similar. CONCLUSIONS: In septic shock, hydrocortisone dosed 75-150 mg/d appears to reverse shock as effectively 200-400 mg/d and may cause a lower frequency of adverse events.

Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.

Recurrence of Gastric Mucosa-associated Lymphoid Tissue Lymphoma in the Pleura: A Case Report.

Mucosa-associated lymphoid tissue (MALT) lymphoma is classified as marginal zone lymphoma, a form of low-grade malignant B-cell non-Hodgkin's lymphoma. It affects the gastrointestinal tract with lung and pleural involvement considered to be rare. We describe a case of a 71-year-old man with a history of MALT lymphoma in remission who presented with dyspnea due to pleural effusion. Pleural fluid flowcytometry analysis showed monotypic B-cell population that expressed cluster of differentiation (CD)19, CD20, CD22, and kappa surface light chains. Medical pleuroscopy and pleural biopsy showed fibroadipose tissue with poorly defined lymphoid aggregates displaying a so-called "monocytoid" appearance, a histologic finding typical of marginal zone lymphoma. The patient underwent pleurodesis and achieved resolution of pleural effusion; however, the patient developed several complications and was discharged on home hospice.

Post-surgical Euglycemic Diabetic Ketoacidosis in a Patient on Empagliflozin in the Intensive Care Unit.

Euglycemic diabetic ketoacidosis (EDKA) is a rare variant of diabetic ketoacidosis which has been recently reported in association with sodium-glucose cotransporter 2 (SGLT-2) inhibitors. Empagliflozin, an agent belonging to this therapeutic class, was approved by the U.S. Food and Drug Administration (FDA) in 2014 for management of type 2 diabetes. Since then, sparse reports of its association with EDKA are emerging, similarly to its predecessors in the class. We report the case of a 58-year-old female who developed EDKA in the intensive care unit (ICU) 48 hours after her last intake of empagliflozin and a day after neurosurgery. Though expected to improve in the post-operative period, she developed a rapidly worsening and unexplained anion gap metabolic acidosis. She was eventually diagnosed with EDKA which was successfully treated with intravenous insulin infusion, dextrose-containing fluids and discontinuation of the offending drug. Metabolic abnormalities improved in less than 24 hours and patient recovered without complications. This report highlights the importance of recognizing EDKA as a complication of oral anti-diabetics and discontinuing SGLT-2 inhibitors days prior to surgery and ICU admission. Care should be applied to providing patient with low-dose ketogenesis-inhibiting basal insulin and close observation of laboratory values in order to minimize delays in diagnosis, prolonged hospital stays and complications of EDKA.

Ivacaftor for the Treatment of Cystic Fibrosis Coexisting with Trisomy 21: A Case Report.

The association between cystic fibrosis (CF) and trisomy 21, or Down Syndrome (DS) is rare, and it pertains a poor prognosis with the majority of patients dying in infancy. We report a case of a 28-year-old male with DS and moderate CF (ΔF508/G551D, FEV1 1.92 L, 60% predicted at the age of 18 years) diagnosed in childhood. The patient's lung function continued to deteriorate over time (FEV1 nadir of 1.29 L), and he was started on ivacaftor in the year 2012 following ivacaftor release and approval. FEV1 and FVC improved significantly along with an increase in the patient's body mass index. Ivacaftor potentiates the open-channel probability of the G551D-CFTR. It has been shown to improve lung function, symptoms, weight, and sweat chloride concentration and decrease the risk of pulmonary exacerbations in patients with severe pulmonary CF (G551D). Our case argues against the reported literature of poor prognosis when the two chronic diseases coexist as only one case report in the literature described a DS patient with CF surviving into adulthood. In our patient, treatment with ivacaftor resulted in an increase in FEV1 and weight that exceeded the response observed in the ivacaftor landmark trial. Genetic studies are underway to understand the genetic basis of the large variation in DS phenotypes, which is probably caused by allelic heterogeneity on multiple chromosomes. The latter may explain the enhanced response observed in our patient and suggests that although patients with concomitant DS and CF may have worse lung disease, their response to novel therapies may be intensified. Further studies are needed in this subset of patient population to better characterize CF with trisomy and other genetic disorders.

Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the same adverse effects as intravenous antibiotics and may prove an alternative in people with poor access to their veins. This is an update of a previously published review. OBJECTIVES: To determine if treatment of pulmonary exacerbations with inhaled antibiotics in people with cystic fibrosis improves their quality of life, reduces time off school or work and improves their long-term survival. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Group's Cystic Fibrosis Trials Register. Date of the last search: 03 October 2018.We searched ClinicalTrials.gov, the Australia and New Zealand Clinical Trials Registry and WHO ICTRP for relevant trials. Date of last search: 09 October 2018. SELECTION CRITERIA: Randomised controlled trials in people with cystic fibrosis with a pulmonary exacerbation in whom treatment with inhaled antibiotics was compared to placebo, standard treatment or another inhaled antibiotic for between one and four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials, assessed the risk of bias in each trial and extracted data. They assessed the quality of the evidence using the GRADE criteria. Authors of the included trials were contacted for more information. MAIN RESULTS: Four trials with 167 participants are included in the review. Two trials (77 participants) compared inhaled antibiotics alone to intravenous antibiotics alone and two trials (90 participants) compared a combination of inhaled and intravenous antibiotics to intravenous antibiotics alone. Trials were heterogenous in design and two were only available in abstract form. Risk of bias was difficult to assess in most trials, but for all trials we judged there to be a high risk from lack of blinding and an unclear risk with regards to randomisation. Results were not fully reported and only limited data were available for analysis.Inhaled antibiotics alone versus intravenous antibiotics aloneOnly one trial (n = 18) reported a perceived improvement in lifestyle (quality of life) in both groups (very low-quality of evidence). Neither trial reported on time off work or school. Both trials measured lung function, but there was no difference reported between treatment groups (very low-quality evidence). With regards to our secondary outcomes, one trial (n = 18) reported no difference in the need for additional antibiotics and the second trial (n = 59) reported on the time to next exacerbation. In neither case was a difference between treatments identified (both very low-quality evidence). The single trial (n = 18) measuring adverse events and sputum microbiology did not observe any in either treatment group for either outcome (very low-quality evidence).Inhaled antibiotics plus intravenous antibiotics versus intravenous antibiotics aloneNeither trial reported on quality of life or time off work or school. Both trials measured lung function, but found no difference between groups in forced expiratory volume in one second (one trial, n = 28, very low-quality evidence) or vital capacity (one trial, n = 62). Neither trial reported on the need for additional antibiotics or the time to the next exacerbation; however, one trial (n = 28) reported on hospital admissions and found no difference between groups. Both trials reported no difference between groups in adverse events (very low-quality evidence) and one trial (n = 62) reported no difference in the emergence of antibiotic-resistant organisms (very low-quality evidence). AUTHORS' CONCLUSIONS: There is little useful high-level evidence to judge the effectiveness of inhaled antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis. The included trials were not sufficiently powered to achieve their goals. Hence, we are unable to demonstrate whether one treatment was superior to the other or not. Further research is needed to establish whether inhaled tobramycin may be used as an alternative to intravenous tobramycin for some pulmonary exacerbations.