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Objective: To evaluate the potential for drug interactions with therapies for pulmonary arterial hypertension (PAH). Treatments include calcium channel blockers, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, guanylate cyclase stimulators, prostacyclin analogues, and prostacyclin receptor agonists. Data Sources: A systemic literature search (January 1980-December 2021) was performed using PubMed and EBSCO to locate relevant articles. The mesh terms used included each specific medication available 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 PAH treatments. The search was limited to those articles studying human applications with PAH treatments 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 PAH treatments are subject to pharmacokinetic and pharmacodynamic interactions. The management of PAH is rapidly evolving. As more and more evidence becomes available for the use of combination therapy in PAH, the increasing use of combination therapy increases the risk of drug-drug interactions. Pulmonary arterial hypertension is also associated with other comorbidities that require concomitant pharmacotherapy. Conclusion: The available literature indicates that PAH therapies are associated with clinically significant drug interactions and the potential for subsequent adverse reactions. Clinicians in all practice settings should be mindful that increased awareness of drug interactions with PAH therapy will ensure optimal management and patient safety.

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 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.

Purpose To provide an updated review of the diagnosis and pharmacotherapy of nontuberculous mycobacteria pulmonary disease (NTM-PD) and summarize guideline recommendations for an interdisciplinary treatment approach. Summary A systemic approach was taken in which all articles in English in MEDLINE and PubMed were reviewed. The US National Library of Medicine's DailyMed database was used to assess drug package inserts. Analysis of NTM treatment guidelines is summarized in the article with a focus on medications, dosing, interactions, and medication monitoring. Conclusion It is critical to manage patients with NTM with a multidisciplinary team approach. Treatment is prolonged and expensive, and the potential for drug toxicity, adverse effects, and drug interactions requires monitoring. Clinical pharmacists play a role in the management of NTM.

Background: Cough characteristics vary between patients, and this can impact clinical diagnosis and care. The purpose of part two of this state-of-the-art review is to update the American College of Chest Physicians (CHEST) 2006 guideline on global physiology and pathophysiology of cough. Study Design and Methods: A review of the literature was conducted using PubMed and MEDLINE databases from 1951 to 2019 using prespecified search terms. Results: We describe the demographics of typical patients with cough in the clinical setting, including how cough characteristics change across age. We summarize the effect of common clinical conditions impacting cough mechanics and the physical properties of mucus on airway clearance. Interpretation: This is the second of a two-part update to the 2006 CHEST cough guideline; it complements part one on basic phenomenology of cough by providing an extended clinical picture of cough along with the factors that alter cough mechanics and efficiency in patients. A greater understanding of the physiology and pathophysiology of cough will improve clinical management.

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.

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.

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

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.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.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 (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.

Background This is an update of the section on complications that are associated with coughing in the 2006 CHEST cough guidelines that addresses two aims: (1) to systematically identify and thematically categorize the diverse complications of cough by providing a guide for future studies and (2) to identify gaps in the literature for future research. Research Question What are the potential complications that are associated with the act of coughing that have been reported in infants, children, adolescents, and adults? Study Design and Methods A scoping review was performed with the use of PubMed and SCOPUS databases that were searched from their beginning until September 6, 2019. Results Two hundred forty-seven publications met our inclusion criteria. To these, we added 38 articles from the 2006 complications paper that were not identified in the literature search plus the paper itself for a final total of 286 publications that formed the basis of this review. Since 2006, three new categories of complications have been reported: ear, nose and throat; disease transmission; and laboratory testing. Multiple additional complications that fall outside of these three categories have also been identified and included in the following categories: cardiovascular, constitutional symptoms, dermatologic, GI, genitourinary, musculoskeletal, neurologic, ophthalmologic, psychosocial/quality of life, and respiratory. Not previously highlighted is that some of the complications led to serious morbidity that included death, especially in patients with comorbid conditions, and potentially resulted in harm to others when cough resulted in a motor vehicle accident. Interpretation Our work identified a large number of cough complications that we thematically categorized primarily by organ system so that future studies of each system or each complication can be conducted. The gap in the literature that future studies should address is to identify the frequency of the complications and the strength of their association with cough. Only then will one be able to describe the findings in a manner that allows specific recommendations for avoiding these complications. In the meantime, patients with cough should be evaluated and treated according to evidence-based guidelines to mitigate or prevent the myriad of potential complications that are associated with coughing.

Background Chronic cough due to chronic bronchitis (CB) causes significant impairment in quality of life, and effective treatment strategies are needed. We conducted a systematic review on the management of chronic cough due to CB to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. Methods This systematic review asked three questions: (1) What are the clinical features of the history that suggest a patient's cough-phlegm syndrome is due to CB? (2) Can treatment of stable CB improve or eliminate chronic cough? (3) Can therapy that targets chronic cough due to CB prevent or reduce the occurrence of acute CB exacerbations? Studies of adult patients with CB were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the CHEST organization methodology. Results The search strategy used an assortment of descriptors and assessments to identify studies of chronic cough due to CB. Conclusions The evidence supporting the management of chronic cough due to CB is limited overall and of low quality. This article provides guidance on treatment by presenting suggestions based on the best currently available evidence and identifies gaps in our knowledge and areas for future research.

Background Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of non-invasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB. Methods We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology. Results Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism. Conclusions This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research.

Background Cough is one of the most common presenting symptoms to general practitioners. The objective of this article is to collate the pediatric components of the CHEST chronic cough guidelines that have recently updated the 2006 guidelines to assist general and specialist medical practitioners in the evaluation and management of children who present with chronic cough. Methods We reviewed all current CHEST Expert Cough Panel's statements and extracted recommendations and suggestions relating to children aged ≤ 14 years with chronic cough (> 4 weeks duration). Additionally, we undertook systematic reviews to update other sections we considered relevant and important. Results The eight recent CHEST guidelines relevant to children, based on systematic reviews, reported some high-quality evidence in the management of chronic cough in children (eg, use of algorithms and management of wet/productive cough using appropriate antibiotics). However, much evidence is still inadequate, particularly in the management of non-specific cough in the community. Conclusions The recommendations and suggestions related to the management of chronic cough in the pediatric age group have been based upon high-quality systematic reviews and are summarized in this article. Compared to the 2006 Cough Guidelines, there is now high-quality evidence for some aspects of the management of chronic cough in children. However, further studies particularly in primary health care are required.

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.

Background Evidence for the diagnosis and management of cough due to acute bronchitis in immunocompetent adult outpatients was reviewed as an update to the 2006 "Chronic Cough Due to Acute Bronchitis: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines." Methods Acute bronchitis was defined as an acute lower respiratory tract infection manifested predominantly by cough with or without sputum production, lasting no more than 3 weeks with no clinical or any recent radiographic evidence to suggest an alternative explanation. Two clinical population, intervention, comparison, outcome questions were addressed by systematic review in July 2017: (1) the role of investigations beyond the clinical assessment of patients presenting with suspected acute bronchitis, and (2) the efficacy and safety of prescribing medication for cough in acute bronchitis. An updated search was undertaken in May 2018. Results No eligible studies relevant to the first question were identified. For the second question, only one relevant study met eligibility criteria. This study found no difference in number of days with cough between patients treated with an antibiotic or an oral nonsteroidal antiinflammatory agent compared with placebo. Clinical suggestions and research recommendations were made based on the consensus opinion of the CHEST Expert Cough Panel. Conclusions The panelists suggested that no routine investigations be ordered and no routine medications be prescribed in immunocompetent adult outpatients first presenting with cough due to suspected acute bronchitis, until such investigations and treatments have been shown to be safe and effective at making cough less severe or resolve sooner. If the cough due to suspected acute bronchitis persists or worsens, a reassessment and consideration of targeted investigations should be considered.

Background:The evolution of compliance and driving pressure in acute respiratory distress syndrome (ARDS) and the effects of time spent on noninvasive respiratory support prior to intubation has not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (i.e., 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: Retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one a rural magnet hospital, and three suburban community facilities. A total of 589 patients were included: 55 COVID-19 positive, 137 culture positive, and 397 culture negative patients. Static compliance and driving pressure were calculated at each 8-hour ventilator check. Results:Days of pre-intubation noninvasive respiratory support was associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19 positive patients showed non-statistically significant worsening compliance by 0.08-units per ventilator check (p = .241), whereas COVID-19 negative patients who were either culture positive or negative patients showed statistically significant improvement (0.12 and 0.18, respectively; both p < .05); a statistically similar but inverse pattern was observed for driving pressure. ConclusionIn contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static lung 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.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone. Summary The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature-infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis-associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, pulmonary vasodilators) lack efficacy or cause harm. Conclusion With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients.

Background Whether gastroesophageal reflux (GER) or GER disease (GERD) causes chronic cough in children is controversial. Using the Population, Intervention, Comparison, Outcome (PICO) format, we undertook four systematic reviews. For children with chronic cough (> 4-weeks duration) and without underlying lung disease: (1) who do not have gastrointestinal GER symptoms, should empirical treatment for GERD be used? (2) with gastrointestinal GER symptoms, does treatment for GERD resolve the cough? (3) with or without gastrointestinal GER symptoms, what GER-based therapies should be used and for how long? (4) if GERD is suspected as the cause, what investigations and diagnostic criteria best determine GERD as the cause of the cough? Methods We used the CHEST Expert Cough Panel's protocol and American College of Chest Physicians (CHEST) methodological guidelines and GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Delphi methodology was used to obtain consensus. Results Few randomized controlled trials addressed the first two questions and none addressed the other two. The single meta-analysis (two randomized controlled trials) showed no significant difference between the groups (any intervention for GERD vs placebo for cough resolution; OR, 1.14; 95% CI, 0.45-2.93; P = .78). Proton pump inhibitors (vs placebo) caused increased serious adverse events. Qualitative data from existing CHEST cough systematic reviews were consistent with two international GERD guidelines. Conclusions The panelists endorsed that: (1) treatment(s) for GERD should not be used when there are no clinical features of GERD; and (2) pediatric GERD guidelines should be used to guide treatment and investigations.

Background The decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation. The current guideline focuses on making the clinical diagnosis of pertussis-associated cough in adults and children. Methods The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on findings from a systematic review that was recently published on the topic; final grading was reached by consensus according to Delphi methodology. The systematic review was carried out to answer the Key Clinical Question: In patients presenting with cough, how can we most accurately diagnose from clinical features alone those who have pertussis-associated cough as opposed to other causes of cough? Results In adults, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 4 clinical features: paroxysmal cough, post-tussive vomiting, inspiratory whooping, and absence of fever. Both paroxysmal cough and absence of fever had high sensitivity (93.2% [95% CI, 83.2-97.4] and 81.8% [95% CI, 72.2-88.7], respectively) and low specificity (20.6% [95% CI, 14.7-28.1] and 18.8% [95% CI, 8.1-37.9]). Inspiratory whooping and posttussive vomiting had a low sensitivity (32.5% [95% CI, 24.5-41.6] and 29.8% [95% CI, 18.0-45.2]) but high specificity (77.7% [95% CI, 73.1-81.7] and 79.5% [95% CI, 69.4-86.9]). In children, after pre-specified meta-analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 1 clinical feature in children (0-18 years): posttussive vomiting. Posttussive vomiting in children was only moderately sensitive (60.0% [95% CI, 40.3-77.0]) and specific (66.0% [95% CI, 52.5-77.3]). Conclusions In adults with acute (

Background Patients commonly present to primary care services with upper and lower respiratory tract infections, and guidelines to help physicians investigate and treat acute cough due to suspected pneumonia and influenza are needed. Methods A systematic search was carried out with eight patient, intervention, comparison, outcome questions related to acute cough due to suspected pneumonia or influenza. Results There was a lack of randomized controlled trials in the setting of outpatients presenting with acute cough due to suspected pneumonia or influenza who were not hospitalized. Both clinical suggestions and research recommendations were made on the evidence available and CHEST Expert Cough Panel advice. Conclusions For outpatient adults with acute cough due to suspected pneumonia, we suggest the following clinical symptoms and signs are suggestive of pneumonia: cough; dyspnea; pleural pain; sweating, fevers, or shivers; aches and pains; temperature ≥ 38°C; tachypnea; and new and localizing chest examination signs. Those suspected of having pneumonia should undergo chest radiography to improve diagnostic accuracy. Although the measurement of C-reactive protein levels strengthens both the diagnosis and exclusion of pneumonia, there was no added benefit of measuring procalcitonin levels in this setting. We suggest that there is no need for routine microbiological testing. We suggest the use of empiric antibiotics according to local and national guidelines when pneumonia is suspected in settings in which imaging cannot be performed. Where there is no clinical or radiographic evidence of pneumonia, we do not suggest the routine use of antibiotics. There is insufficient evidence to make recommendations for or against specific nonantibiotic, symptomatic therapies. Finally, for outpatient adults with acute cough and suspected influenza, we suggest that initiating antiviral treatment (according to Centers for Disease Control and Prevention advice) within 48 hours of symptoms could be associated with decreased antibiotic use and hospitalization and improved outcomes.

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.Is prolonged prehospital time an independent risk factor for pneumonia?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.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.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.

Objective The purpose of this narrative review was to provide guidance for pharmacists concerning vitamin D supplementation. Methods Relevant studies were identified in a search of MEDLINE/PubMed, EBSCOhost, and Google Scholar from January 1966 to September 2020 using the search terms vitamin D, vitamin D2, vitamin D3, calcitriol, and vitamin D deficiency. Abstracts were reviewed for relevance and, if relevant, full-text articles were retrieved and reviewed. References were checked, and citation searches using identified studies were conducted. The literature search included English-language studies involving administration of vitamin D monotherapy compared with placebo. Results Serum 25–hydroxyvitamin D levels of less than 12 ng/mL indicate a vitamin D deficiency. The Institute of Medicine recommends a daily intake of 600 IU of vitamin D in individuals aged up to 70 years and 800 IU in those aged above 70 years. Vitamin D is labeled for rickets, osetomalacia, hypophosphatemia (familial or secondary), renal osteodystrophy, and corticosteroid-induced osteoporosis. When used for these indications, vitamin D should be prescribed with appropriate monitoring by a qualified health care practitioner. There is evidence for vitamin D supplementation in individuals aged 75 years or older and in those with problems associated with mobility, gait, or balance. There is insufficient evidence to support vitamin D supplementation in the prevention of cardiovascular disease, cancer, asthma, chronic obstructive pulmonary disease exacerbations, new-onset type 2 diabetes, infectious lung diseases, cognitive dysfunction, Alzheimer disease, and depression, or in prenatal use. Conclusion Pharmacists can provide evidence-based recommendations concerning the indications, dosing, monitoring, and adverse effects of vitamin D supplements.

BackgroundIntravenous (IV) acetaminophen is used in multimodal analgesia to reduce the amount and duration of opioid use in the postoperative setting.MethodsA systematic review of published randomized controlled trials was conducted to define the opioid-sparing effect of IV acetaminophen in different types of surgeries. Eligible studies included prospective, randomized, double-blind trials of IV acetaminophen compared with either a placebo- or active-treatment group in adult (age ≥18 years) patients undergoing surgery. Trials had to be published in English in a peer-reviewed journal.ResultsA total of 44 treatment cohorts included in 37 studies were included in the systematic analysis. Compared with active- or placebo-control treatments, IV acetaminophen produced a statistically significant opioid-sparing effect in 14 of 44 cohorts (32%). An opioid-sparing effect was more common in placebo-controlled comparisons. Of the 28 placebo treatment comparisons, IV acetaminophen produced an opioid-sparing effect in 13 (46%). IV acetaminophen produced an opioid-sparing effect in only 6% (one out of 16) of the active-control groups. Among the 16 active-control groups, opioid consumption was significantly greater with IV acetaminophen than the active comparator in seven cohorts and not significantly different than the active comparator in eight cohorts.ConclusionsThe results of this systematic analysis demonstrate that IV acetaminophen is not effective in reducing opioid consumption compared with other adjuvant analgesic agents in the postoperative patient. In patients where other adjuvant analgesic agents are contraindicated, IV acetaminophen may be an option.

Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking.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?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).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.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.

Background Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. Methods This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough ≥ 8 weeks' duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. Results Eight randomized controlled trials and two case series (≥ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma-related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma-associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. Conclusions The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed.

Background Acute bronchiolitis is common in young children, and some children develop chronic cough after their bronchiolitis. We thus undertook systematic reviews based on key questions (KQs) using the PICO (Population, Intervention, Comparison, Outcome) format. The KQs were: Among children with chronic cough (> 4 weeks) after acute viral bronchiolitis, how effective are the following interventions in improving the resolution of cough?: (1) Antibiotics. If so what type and for how long? (2) Asthma medications (inhaled steroids, beta2 agonist, montelukast); and (3) Inhaled osmotic agents like hypertonic saline? Methods We used the CHEST expert cough panel's protocol and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients' values and preferences and the clinical context were used to form these suggestions. Delphi methodology was used to obtain consensus. Results Several studies and systematic reviews on the efficacy of the three types of interventions listed in the introduction were found but no data were relevant to our KQs. Thus, no recommendations on using the interventions above could be formulated. Conclusions The panel made several consensus-based suggestions and identified directions for future studies to advance the field of managing chronic cough post-acute bronchiolitis in children.

Objective: To evaluate the potential for drug interactions with oral inhaled medications (OIMs). OIMs include bronchodilators (β-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.

Background Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. Methods A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Results Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. Conclusions On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO-endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost-effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.

Background We performed systematic reviews using the population, intervention, comparison, outcome (PICO) format to answer the following key clinical question: Are the CHEST 2006 classifications of acute, subacute and chronic cough and associated management algorithms in adults that were based on durations of cough useful? Methods We used the CHEST Expert Cough Panel's protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patient values and preferences and the clinical context were used to form recommendations or suggestions. Delphi methodology was used to obtain the final grading. Results With respect to acute cough ( 8 weeks), 11 studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were UACS from rhinosinus conditions, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, combinations of these four conditions, and, less commonly, a variety of miscellaneous conditions and atopic cough in Asian countries. The subjects resided on four continents: North America, South America, Europe, and Asia. Conclusions Although the quality of evidence was low, the published literature since 2006 suggests that CHEST's 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017.

Background Cough is a common symptom prompting patients to seek medical care. Like patients in the general population, patients with compromised immune systems also seek care for cough. However, it is unclear whether the causes of cough in immunocompromised patients who are deemed unlikely to have a life-threating condition and a normal or unchanged chest radiograph are similar to those in persons with cough and normal immune systems. Methods We conducted a systematic review to answer the question: What are the most common causes of cough in ambulatory immunodeficient adults with normal chest radiographs? Studies of patients ≥ 18 years of age with immune deficiency, cough of any duration, and normal or unchanged chest radiographs were included and assessed for relevance and quality. Based on the systematic review, suggestions were developed and voted on using the American College of Chest Physicians (CHEST) methodology framework. Results The results of the systematic review revealed no high-quality evidence to guide the clinician in determining the likely causes of cough specifically in immunocompromised ambulatory patients with normal chest radiographs. Conclusions Based on a systematic review, we found no evidence to assess whether or not the proper initial evaluation of cough in immunocompromised patients is different from that in immunocompetent persons. A consensus of the panel suggested that the initial diagnostic algorithm should be similar to that for immunocompetent persons but that the context of the type and severity of the immune defect, geographic location, and social determinants be considered. The major modifications to the 2006 CHEST Cough Guidelines are the suggestions that TB should be part of the initial evaluation of patients with cough and HIV infection who reside in regions with a high prevalence of TB, regardless of the radiographic findings, and that specific causes and immune defects be considered in all patients in whom the initial evaluation is unrevealing.

Background There is no published systematic review on the etiologies of chronic cough or the relationship between OSA and chronic cough in children aged ≤ 14 years. We thus undertook a systematic review based on key questions (KQs) using the Population, Intervention, Comparison, Outcome format. The KQs follow: Among children with chronic (> 4 weeks) cough (KQ 1) are the common etiologies different from those in adults? (KQ 2) Are the common etiologies age or setting dependent, or both? (KQ 3) Is OSA a cause of chronic cough in children? Methods We used the CHEST Expert Cough Panel's protocol and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patients' values and preferences and the clinical context were used to form recommendations. Delphi methodology was used to obtain consensus. Results Combining KQs 1 and 2, we found moderate-level evidence from 10 prospective studies that the etiologies of cough in children are different from those in adults and are setting dependent. Data from three studies found that common etiologies of cough in young children were different from those in older children. However, data relating sleep abnormalities to chronic cough in children were found only in case studies. Conclusions There is moderate-quality evidence that common etiologies of chronic cough in children are different from those in adults and are dependent on age and setting. As there are few data relating OSA and chronic cough in children, the panel suggested that these children should be managed in accordance with pediatric sleep guidelines.

Background Cough among patients with lung cancer is a common but often undertreated symptom. We used a 2015 Cochrane systematic review, among other sources of evidence, to update the recommendations and suggestions of the American College of Chest Physicians (CHEST) 2006 guideline on this topic. Methods The CHEST methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on data from the Cochrane systematic review on the topic, uncontrolled studies, case studies, and the clinical context. Final grading was reached by consensus according to the Delphi method. Results The Cochrane systematic review identified 17 trials of primarily low-quality evidence. Such evidence was related to both nonpharmacologic (cough suppression) and pharmacologic (demulcents, opioids, peripherally acting antitussives, or local anesthetics) treatments, as well as endobronchial brachytherapy. Conclusions Compared with the 2006 CHEST Cough Guideline, the current recommendations and suggestions are more specific and follow a step-up approach to the management of cough among patients with lung cancer, acknowledging the low-quality evidence in the field and the urgent need to develop more effective, evidence-based interventions through high-quality research.

Background Cough is a common symptom experienced by athletes, particularly after exercise. We performed a systematic review to assess the following in this population: (1) the main causes of acute and recurrent cough, either exercise-induced or not, (2) how cough is assessed, and (3) how cough is treated in this population. From the systematic review, suggestions for management were developed. Methods This review was performed according to the CHEST methodological guidelines and Grading of Recommendations Assessment, Development and Evaluation framework until April 2015. To be included, studies had to meet the following criteria: participants had to be athletes and adults and adolescents aged ≥ 12 years and had to complain of cough, regardless of its duration or relationship to exercise. The Expert Cough Panel based their suggestions on the data extracted from the review and final grading by consensus according to a Delphi process. Results Only 60 reports fulfilled the inclusion criteria, and the results of our analysis revealed only low-quality evidence on the causes of cough and how to assess and treat cough specifically in athletes. Although there was no formal evaluation of causes of cough in the athletic population, the most common causes reported were asthma, exercise-induced bronchoconstriction, respiratory tract infection (RTI), upper airway cough syndrome (UACS) (mostly from rhinitis), and environmental exposures. Cough was also reported to be related to exercise-induced vocal cord dysfunction among a variety of less common causes. Although gastroesophageal reflux disease (GERD) is frequent in athletes, we found no publication on cough and GERD in this population. Assessment of the causes of cough was performed mainly with bronchoprovocation tests and suspected disease-specific investigations. The evidence to guide treatment of cough in the athlete was weak or nonexistent, depending on the cause. As data on cough in athletes were hidden in a set of other data (respiratory symptoms), evidence tables were difficult to produce and were done only for cough treatment in athletes. Conclusions The causes of cough in the athlete appear to differ slightly from those in the general population. It is often associated with environmental exposures related to the sport training environment and occurs predominantly following intense exercise. Clinical history and specific investigations should allow identification of the cause of cough as well as targeting of the treatment. Until management studies have been performed in the athlete, current guidelines that exist for the general population should be applied for the evaluation and treatment of cough in the athlete, taking into account specific training context and anti-doping regulations.

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.

Background We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome. Methods Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux? Results We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely. Conclusions The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Background In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected. Methods MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel. Results The literature review identified relevant articles regarding: mechanisms; allergic environmental causes; chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke; nonallergic environmental triggers; laryngeal syndromes; and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature. Conclusions Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.

Background Unexplained chronic cough (UCC) causes significant impairments in quality of life. Effective assessment and treatment approaches are needed for UCC. Methods This systematic review of randomized controlled trials (RCTs) asked: What is the efficacy of treatment compared with usual care for cough severity, cough frequency, and cough-related quality of life in patients with UCC? Studies of adults and adolescents aged > 12 years with a chronic cough of > 8 weeks' duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using the American College of Chest Physicians organization methodology. Results Eleven RCTs and five systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used an assortment of descriptors and assessments to identify UCC. Although gabapentin and morphine exhibited positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) were affected by intervention fidelity bias; when this factor was addressed, ICS were found to be ineffective for UCC. Esomeprazole was ineffective for UCC without features of gastroesophageal acid reflux. Studies addressing nonacid gastroesophageal reflux disease were not identified. A multimodality speech pathology intervention improved cough severity. Conclusions The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology-based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge as well as areas for future research.

Objectives To report 2 cases of lipoid pneumonia. Summary Lipoid pneumonia is an inflammatory process in the lower airways due to the presence of lipid molecules in the alveoli. Exogenous lipoid pneumonia is due to the inhalation or aspiration of fat-containing substances. Historically, mineral oil is the most common medication cause but there have also been several reports of lipoid pneumonia associated with petroleum jelly, medicated vapor rub, and lip glosses. Two case reports are presented to illustrate the importance of identifying risk factors for lipoid pneumonia. Results Use of the Naranjo algorithm suggested that both cases of lipoid pneumonia were "possibly" due to aspiration of lipid-containing over-the-counter agents. The first case was associated with aspiration of mentholated topical ointment applied intranasally, whereas the second case was attributed to probable aspiration of mineral oil for management of chronic constipation. Conclusion Pharmacists in many practice settings can play an integral role in preventing this condition and screening for patients who may warrant a diagnostic workup. During medication reconciliation, pharmacists should identify all prescription and nonprescription medications used by patients. Patients should specifically be asked about lipid-based over-the-counter products and cosmetic agents.