A Retrospective Analysis of the Effects of Time on Compliance and Driving Pressures in ARDS.

BACKGROUND: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. METHODS: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment. RESULTS: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment (P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure. CONCLUSIONS: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

Prolonged Prehospital Time Is a Risk Factor for Pneumonia in Trauma (the PRE-TRIP Study): A Retrospective Analysis of the United States National Trauma Data Bank.

BACKGROUND: Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown. RESEARCH QUESTION: Is prolonged prehospital time an independent risk factor for pneumonia? STUDY DESIGN AND METHODS: We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016. RESULTS: Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P < .001). This association was primarily driven by patients with low Glasgow Coma Scale scores. Post-trauma pneumonia was uncommon (1.5% incidence) but was associated with a significant increase in mortality (P < .001, 4.3% mortality without pneumonia vs 12.1% mortality with pneumonia). Other pneumonia risk factors included age, sex, race, primary payor, trauma center teaching status, bed size, geographic region, intoxication, comorbid lung disease, steroid use, lower Glasgow Coma Scale score, higher Injury Severity Scale score, blood product transfusion, chest trauma, and respiratory burns. INTERPRETATION: Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making.

C-reactive protein levels associated with COVID-19 outcomes in the United States.

CONTEXT: COVID-19 caused a worldwide pandemic, and there are still many uncertainties about the disease. C-reactive protein (CRP) levels could be utilized as a prognosticator for disease severity in COVID-19 patients. OBJECTIVES: This study aims to determine whether CRP levels are correlated with COVID-19 patient outcomes and length of stay (LoS). METHODS: A retrospective cohort study was conducted utilizing data obtained between March and May 2020. Data were collected by abstracting past medical records through electronic medical records at 10 hospitals within CommonSpirit Health. Patients were included if they had a positive COVID-19 test from a nasopharyngeal swab sample, and if they were admitted and then discharged alive or had in-hospital mortality and were ≥18 years. A total of 541 patients had CRP levels measured and were included in this report. Patient outcome and LoS were the endpoints measured. RESULTS: The 541 patients had their CRP levels measured, as well as the demographic and clinical data required for analysis. While controlling for body mass index (BMI), number of comorbidities, and age, the first CRP was significantly predictive of mortality (p<0.001). The odds ratio for first CRP indicates that for each one-unit increase in CRP, the odds of death increased by 0.007. For LoS, the first CRP was a significant predictor (p<0.001), along with age (p=0.002). The number of comorbidities also predicted LoS (p=0.007), but BMI did not. The coefficient for the first CRP indicates that, for each one-unit increase in CRP, LoS increased 0.003 days. CONCLUSIONS: The results indicate that there is a positive correlation between the CRP levels of COVID-19 patients and their respective outcomes with regard to death and LoS.

Radial endobronchial ultrasound-assisted transbronchial needle aspiration for pulmonary peripheral lesions in the segmental bronchi adjacent to the central airway.

BACKGROUND: Tissue samples from lesions located in the 3rd to 5th segmental bronchi are challenging to obtain. In this retrospective study, we aimed to evaluate the diagnostic rate of pulmonary peripheral lesions located in the 3rd to 5th segmental bronchi, near the inner field of lung on the computed tomography (CT) image and outside the bronchus, using radial endobronchial ultrasound (REBUS) followed by transbronchial needle aspiration (TBNA). METHODS: This retrospective study enrolled patients whose preoperative CT examinations showed a lesion located in the segmental bronchi (3rd to 5th), yet adjacent to the inner field of lung on the CT image. REBUS followed by TBNA was used to acquire tissue samples from these lesions. A bronchoscope was used to reach the bronchi surrounding the lesion, and an ultrasound probe was used to determine the lesion's location. Then, the ultrasound probe was withdrawn, and puncture was performed at the location that was determined by ultrasound. The tissue specimens obtained were subjected to pathological examination. RESULTS: Nineteen patients were enrolled in this study including 15 males and 4 females with an average age of 55 years old. Of the enrollees, 8 patients (42.1%) were successfully diagnosed with samples obtained through TBNA, including 6 cases of lung cancer, 1 case of non-specific inflammation, and 1 case of cryptococcal infection. The diagnostic rate was 42.1%. No post-procedural complications were observed among the patients. There was no significant difference in nodule diameter between patients with a diagnostic sample and those in whom TBNA failed to provide a diagnosis (2.99±0.96 vs. 2.26±1.27 cm, P=0.20). CONCLUSIONS: With the assistance of REBUS, TBNA can acquire sufficient samples to achieve a reasonably diagnostic rate for parenchymal lung lesions located near the inner field of lung on the CT image without intrabronchial invasion.

Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial.

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]). Key innovations of this trial include 1) a novel smartphone-based communication process that facilitates rapid enrollment and intervention delivery while allowing social distancing and conservation of personal protective equipment, 2) Bayesian response-adaptive randomization to allow preferential assignment to the most effective intervention and expedite trial completion compared with frequentist designs, 3) remote electronic collection of patient-reported outcomes and electronic medical record data, and 4) pragmatic prospective use of patient-reported data and data collected as part of routine clinical care. Clinical trial registered with www.clinicaltrials.gov (NCT04344587).

Sympathetic stimulation increases serum lactate concentrations in patients admitted with sepsis: implications for resuscitation strategies.

BACKGROUND: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. METHODS: Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. RESULTS: MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. CONCLUSIONS: In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Pulmonary Manifestations of Rheumatoid Arthritis.

OBJECTIVE: To describe the case of an 88-yearold male with rheumatoid arthritis who developed pulmonary manifestations. Treatment for his RA previously included various biologics, while at the time of pulmonary consultation included meloxicam, methotrexate, and abatacept. Following chest scans, bronchoscopy, needle biopsy, pulmonary function testing, and a thoracentesis, the diagnosis of pleural effusion and nodules associated with rheumatoid arthritis was determined. The patient was recommended to follow-up with the pulmonologist but was lost to follow-up because of nonpulmonary and nonrheumatoid arthritis complications.
SETTINGS: Ambulatory clinic pharmacy practice, Community pharmacy, Consultant pharmacy practice.
PRACTICE CONSIDERATIONS: Drugs used to treat rheumatoid arthritis may produce pulmonary toxicity similar to what is seen with the disease itself. Drug therapy may require modification if identified as an offending agent causing pulmonary manifestations. If fibrosing interstitial lung disease develops, the addition of nintedanib may need to be considered.
CONCLUSION: In order for pharmacists to better assist providers and patients and improve therapeutic outcomes, it is important for pharmacists to understand that pulmonary manifestations are common in patients having rheumatoid arthritis as well as with drugs used to treat rheumatoid arthritis.

Sepsis, the Administration of IV Fluids, and Respiratory Failure: A Retrospective Analysis-SAIFR Study.

BACKGROUND: Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking. RESEARCH QUESTION: Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg? STUDY DESIGN AND METHODS: This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD). RESULTS: A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups. INTERPRETATION: In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure.

The POSITIONED Study: Prone Positioning in Nonventilated Coronavirus Disease 2019 Patients-A Retrospective Analysis.

Given perceived similarities between coronavirus disease 2019 pneumonia and the acute respiratory distress syndrome, we explored whether awake self-proning improved outcomes in coronavirus disease 2019-infected patients treated in a rural medical center with limited resources during a significant local coronavirus disease 2019 outbreak. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Single-center rural community-based medical center in Grand Island, NE. PATIENTS: One hundred five nonintubated, coronavirus disease-infected patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After patients were educated on the benefits of awake self-proning, compliance was voluntary. The primary outcome was need for intubation during the hospital stay; secondary outcomes included serial peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios, in-hospital mortality, and discharge disposition. Of 105 nonintubated, coronavirus disease-infected patients, 40 tolerated awake self-proning. Patients who were able to prone were younger and had lower disease severity. The risk of intubation was lower in proned patients after adjusting for disease severity using Sequential Organ Failure Assessment scores (adjusted hazard ratio, 0.30; 95% CI, 0.09-0.96; p = 0.043) or Acute Physiology and Chronic Health Evaluation II scores (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.91; p = 0.034). No prone patient died compared with 24.6% of patients who were not prone (p < 0.001; number needed to treat = 5; 95% CI, 3-8). The probability of being discharged alive and peripheral capillary oxygen saturation measured by pulse oximetry to the Fio2 ratios were statistically similar for both groups. CONCLUSIONS: Awake self-proning was associated with lower mortality and intubation rates in coronavirus disease 2019-infected patients. Prone positioning appears to be a safe and inexpensive strategy to improve outcomes and spare limited resources. Prospective efforts are needed to better delineate the effect of awake proning on oxygenation and to improve patients' ability to tolerate this intervention.

Review of Cases of E-Cigarette or Vaping Product Use-Associated Lung Injury (EVALI) and Brief Review of the Literature.

Since the appearance of the E-Cigarette in the early 2000s, its industry, popularity, and prevalence have risen dramatically. In the past, E-Cigarette use with the vaping of nicotine or cannabis products had been associated with a few reported cases of lung injury. However, in 2019, thousands of cases of E-Cigarette or vaping product use-associated lung injury (EVALI) were reported in the United States. Evidence linked this outbreak with vaping of tetrahydrocannabinol (THC). We report two confirmed cases of EVALI and their associated clinical, radiologic, and pathologic features. This report supports the growing body of information regarding EVALI. It also discusses various substances, particularly vitamin E acetate, which has been suggested as a causative agent.

Sepsis and the Obesity Paradox: Size Matters in More Than One Way.

OBJECTIVES: Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure. DESIGN: Retrospective analysis of prospectively collected clinical data. SETTING: Five community-based and one academic medical center in the Omaha, NE. PATIENTS: 7,967 adults hospitalized with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate. CONCLUSIONS: Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Diffuse Alveolar Hemorrhage Following Pirfenidone Initiation.

INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is bleeding into the alveolar space of the lungs. Pirfenidone is an antifibrotic agent that is approved for the treatment of idiopathic pulmonary fibrosis (IPF). The most commonly reported side effects include gastrointestinal and skin-related events. We present 3 cases of hemoptysis and DAH among patients on pirfenidone therapy for IPF. CASE SUMMARIES: An 88-year-old female, a 75-year-old male, and a 73-year-old male all with IPF on pirfenidone presented with hemoptysis and chest computed tomography (CT) findings of usual interstitial pneumonia (UIP) with superimposed opacities. In 2 patients, DAH was confirmed with bronchoscopy. Corticosteroids were initiated and pirfenidone discontinued in all patients, and 2 patients improved while the third continued to deteriorate. Nintedanib was initiated in the remaining 2 patients at follow-up visit with no further issues. DISCUSSION: IPF is a chronic, progressive, fibrotic interstitial lung disease (ILD) which appears to be increasing in the United States and has a relatively short survival. Nintedanib and pirfenidone were the first Food and Drug Administration (FDA)-approved agents for the treatment of IPF in October 2014. We present 3 cases of DAH in patients with IPF receiving pirfenidone. Symptoms occurred within 2 months of pirfenidone initiation and resolved with discontinuation of pirfenidone and initiation of systemic corticosteroids in 2 patients; however, one case was complicated by concomitant discontinuation of aspirin. The mechanism by which DAH occurred in our patients remains unclear. CONCLUSION: We report the first cases of possible pirfenidone-induced DAH. Further studies are warranted to explore this reaction, but prescribers should be cognizant of this potential issue when choosing to prescribe pirfenidone.

The Impact of Gravity vs Suction-driven Therapeutic Thoracentesis on Pressure-related Complications: The GRAVITAS Multicenter Randomized Controlled Trial.

BACKGROUND: Thoracentesis can be accomplished by active aspiration or drainage with gravity. This trial investigated whether gravity drainage could protect against negative pressure-related complications such as chest discomfort, re-expansion pulmonary edema, or pneumothorax compared with active aspiration. METHODS: This prospective, multicenter, single-blind, randomized controlled trial allocated patients with large free-flowing effusions estimated ≥ 500 mL 1:1 to undergo active aspiration or gravity drainage. Patients rated chest discomfort on 100-mm visual analog scales prior to, during, and following drainage. Thoracentesis was halted at complete evacuation or for persistent chest discomfort, intractable cough, or other complication. The primary outcome was overall procedural chest discomfort scored 5 min following the procedure. Secondary outcomes included measures of discomfort and breathlessness through 48 h postprocedure. RESULTS: A total of 142 patients were randomized to undergo treatment, with 140 in the final analysis. Groups did not differ for the primary outcome (mean visual analog scale score difference, 5.3 mm; 95% CI, -2.4 to 13.0; P = .17). Secondary outcomes of discomfort and dyspnea did not differ between groups. Comparable volumes were drained in both groups, but the procedure duration was significantly longer in the gravity arm (mean difference, 7.4 min; 95% CI, 10.2 to 4.6; P < .001). There were no serious complications. CONCLUSIONS: Thoracentesis via active aspiration and gravity drainage are both safe and result in comparable levels of procedural comfort and dyspnea improvement. Active aspiration requires less total procedural time. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03591952; URL: www.clinicaltrials.gov.

Waste not, want not: diagnostic material found in suction syringe aspirate during endobronchial ultrasound guided transbronchial needle aspiration.

BACKGROUND: Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a frequently performed procedure. Suction is utilized during this procedure and may occasionally result in the collection of aspirated material, the diagnostic utility of which is uncertain. This study aims to determine the contents of the suction syringe aspirate and its diagnostic value. METHODS: The suction syringe aspirate was pooled in a container and sent for analysis. We retrospectively reviewed the cytological outcomes of these specimens in comparison to the diagnosis determined by EBUS-TBNA between 2015-2018. The primary outcome was the percent agreement between the diagnostic material found in the suction syringe aspirate, and the final diagnosis established by EBUS-TBNA. RESULTS: Forty-four patients were included. Percent agreement was calculated as the percent in which the suction syringe aspirate diagnosis agreed with the EBUS-TBNA diagnosis. The percent agreement of any diagnosis was 90.9% (95% CI: 78.7-97.2%). Two of the 44 diagnoses (4.5%) were established based solely on the suction syringe aspirate, both cases of granulomatous inflammation. CONCLUSIONS: Our results suggest that material collected in the suction syringe has a very high percent agreement with the final diagnosis established by EBUS-TBNA. Furthermore, the suction syringe aspirate may represent the sole diagnostic material in nearly 5% of cases. Given the additional diagnostic material in the suction syringe aspirate, it is reasonable to pool the aspirate with the primary specimen in an effort to enrich the overall diagnostic specimen. This practice may improve the likelihood that the specimen will be sufficient for additional molecular analysis, although further study is necessary. Care must be taken when more than one needle is involved to ensure that a new suction syringe is also used to avoid inadvertent upstaging by specimen contamination.

A 75 year old male with recurrent unilateral pleural effusion and positive ANA.

This case report describes the clinical course and diagnostic challenges arising in a 75 year old man who initially presented with progressive shortness of breath. Imaging revealed a pleural effusion, which was recurrent following thoracentesis. While his initial workup suggested an autoimmune etiology, further diagnostic testing revealed a diagnosis of malignant pleural mesothelioma. Curiously, the patient had no known asbestos exposure, which is classically associated with acquired mesothelioma. There are a small number of similar cases with a possible overlap between positive autoimmune serologies and mesothelioma; however, the underlying pathophysiology remains elusive. It is the authors' goal to contribute this case to the few cases describing such overlap syndromes.

Drug Interactions With Oral Inhaled Medications.

Objective: To evaluate the potential for drug interactions with oral inhaled medications (OIMs). OIMs include bronchodilators (ß-agonists and antimuscarinics), corticosteroids, combination products (2 or more agents combined within a single inhalation device), antibiotics, prostacyclins, anesthetics, acetylcysteine, mucolytics, insulin, antivirals, nitric oxide, and nicotine replacement. Data Sources: A systemic literature search (1980 to May 2018) was performed using PubMed and EBSCO to locate relevant articles. The MESH terms used included each specific medication available as an OIM as well as "drug interactions." DAILYMED was used for product-specific drug interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with OIMs. The search was limited to those articles studying human applications with OIMs and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that OIMs are subject to pharmacokinetic and pharmacodynamics interactions. The most frequently identified clinically significant drug interaction is an inhaled corticosteroid when combined with a potent CYP 450 inhibitor such as a protease inhibitor or antifungal. Conclusions: The available literature indicates that OIMs are associated with clinically significant drug interactions and subsequent adverse reactions. Clinicians in all practice settings should be mindful of this potential to minimize adverse effects and optimize therapy.