Andrew Skabelund

Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

BackgroundWe have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan.MethodsForty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid.ResultsOver seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency.ConclusionsCandidate proteins and miRNAs associated with the general diagnosis of dyspnea have been identified in subjects with differing medical diagnoses. Since these markers can be measured in readily obtained clinical samples, further studies are possible that test the value of these findings in more formal classification or case–control studies in much larger cohorts of subjects with specific lung diseases such as asthma, emphysema, or some other well-defined lung disease.

Chronic Pulmonary Blastomycosis Mimicking Pulmonary Tuberculosis

Introduction Blastomyces dermatitidis is a dimorphic fungus endemic to the Mississippi River valley. We describe a rare case of chronic pulmonary blastomycosis complicated by large pulmonary cavitation in a young service member who was misdiagnosed with active pulmonary tuberculosis. Case Presentation A 25-year-old active duty male presented to his primary care provider with complaints of hemoptysis, fatigue, weight loss, and fever. Computed tomography chest with contrast identified a large cavitary lesion in the right upper lobe (RUL). The patient was admitted to an outside hospital and he underwent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage of the RUL. Histology and cultures were unremarkable however; Histoplasma serum antigen was positive. The patient was empirically treated for active pulmonary tuberculosis and soon discharged. He returned for medical evaluation 3 mo later with continued hemoptysis. Repeat bronchoscopy with transbronchial biopsies of the RUL cavity grew Blastomyces dermatitidis. The patients symptoms resolved and chest imaging significantly improved with initiation of itraconazole. Discussion Chronic pulmonary blastomycosis can present with a constellation of symptoms that may be indistinguishable from chronic pulmonary histoplasmosis, pulmonary tuberculosis, or lung cancer. Knowledge of endemic diseases and a thorough travel history should be an integral part of a military physicians infectious disease evaluation.

Procalcitonin, erythrocyte sedimentation rate and C-reactive protein in acute pulmonary exacerbations of cystic fibrosis

Acute pulmonary exacerbations of cystic fibrosis (APECF) are a leading cause of morbidity and mortality among patients with cystic fibrosis (CF). APECF require frequent administration of antibiotics and subsequently lead to development of resistant organisms.

Effect of a pulmonary nodule fact sheet on patient anxiety and knowledge: a quality improvement initiative

Introduction The utilisation of chest CT for the evaluation of pulmonary disorders, including low-dose CT for lung cancer screening, is increasing in the USA. As a result, the discovery of both screening-detected and incidental pulmonary nodules has become more frequent. Despite an overall low risk of malignancy, pulmonary nodules are a common cause of emotional distress among adult patients. Methods We conducted a multi-institutional quality improvement (QI) initiative involving 101 participants to determine the effect of a pulmonary nodule fact sheet on patient knowledge and anxiety. Males and females aged 35 years or older, who had a history of either screening-detected or incidental solid pulmonary nodule(s) sized 3–8 mm, were included. Prior to an internal medicine or pulmonary medicine clinic visit, participants were given a packet containing a pre-fact sheet survey, a pulmonary nodule fact sheet and a post-fact sheet survey. Results Of 101 patients, 61 (60.4%) worried about their pulmonary nodule at least once per month with 18 (17.8%) worrying daily. The majority 67/101 (66.3%) selected chemotherapy, chemotherapy and radiation, or radiation as the best method to cure early-stage lung cancer. Despite ongoing radiographic surveillance, 16/101 (15.8%) stated they would not be interested in an intervention if lung cancer was diagnosed. Following review of the pulmonary nodule fact sheet, 84/101 (83.2%) reported improved anxiety and 96/101 (95.0%) reported an improved understanding of their health situation. Patient understanding significantly improved from 4.2/10.0 to 8.1/10.0 (p<0.01). Conclusion The incorporation of a standardised fact sheet for subcentimeter solid pulmonary nodules improves patient understanding and alleviates anxiety. We plan to implement pulmonary nodule fact sheets into the care of our patients with low-risk subcentimeter pulmonary nodules.

Does Global Lung Initiative Obviate the Need for Lung Volume Measurements

Establishing the diagnosis of restrictive lung disease is often difficult and requires extensive testing not only to diagnose but also to accurately classify the underlying disease. Current clinical practice often involves an initial screening with spirometry and a subsequent measurement of the

Pulmonary Function and Respiratory Health of Military Personnel Before Southwest Asia Deployment

BACKGROUND: Significant concern exists regarding the respiratory health of military personnel deployed to Southwest Asia, given their exposures to numerous environmental hazards. Although the deployed military force is generally assumed to be fit, the pre-deployment respiratory health of these individuals is largely unknown. METHODS: Soldiers deploying to Southwest Asia were recruited from the pre-deployment processing center at Fort Hood, Texas. Participants completed a general and respiratory health questionnaire and performed baseline spirometry. RESULTS: One thousand six hundred ninety-three pre-deployment evaluations were completed. The average age of the participants was 32.2 y, and 83.1% were male. More than one third of surveyed solders had a smoking history, 73% were overweight or obese, and 6.2% reported a history of asthma. Abnormal spirometry was found in 22.3% of participants. Soldiers with abnormal spirometry reported more asthma (10.1% vs 5.1%, P < .001), failed physical fitness tests (9.0% vs 4.6%, P = .02), and respiratory symptoms (32.8% vs 24.3%, P = .001). DISCUSSION: This is the first prospective pre-deployment evaluation of military personnel that delineates factors potentially associated with the development of pulmonary symptoms and/or disease. This study suggests that deploying soldiers are older, heavier, frequently smoke, and may have undiagnosed pre-deployment lung disease. Abnormal spirometry is common but may not represent underlying disease. Self-reported asthma, wheezing, and slower 2-mile run times were predictive of abnormal spirometry. CONCLUSIONS: Pre-deployment evaluation of military personnel identified numerous soldiers with active pulmonary symptoms and abnormal spirometry. When combined with questions regarding asthma history, wheezing and exercise intolerance, spirometry may identify individuals at risk for deployment-related respiratory complaints.

Impact of High Altitude on Military Operations

Purpose of ReviewHigh-altitude combat and medical evacuation pose special challenges to military operations. We aim to summarize the physiologic changes that occur at altitude, as well as review the altitude-related diseases with emphasis on the impact on the military population. Finally, the impact of high-altitude exposure during transportation of combat trauma will be reviewed.Recent FindingsThere is increasing awareness that high-altitude exposure has an impact on mission readiness and could place mission success at risk. High-altitude headache and acute mountain sickness have affected warfighters in both training and combat. Prophylaxis of altitude illness with acetazolamide has been shown to reduce symptoms of altitude exposure; dexamethasone is utilized for the same purpose.Though not without risk, long-range high-altitude transport of critically ill trauma and medical patients has been found to be safe and effective.SummaryHypobaric hypoxia is the primary driving force behind the physiologic effects altitude has on the human body. When combined with the stress of combat and AE, altitude can pose a difficult obstacle when caring for critically ill patients. Awareness of altitude-related disease and its impact when caring for non-altitude-related illness is a crucial component of optimizing healthcare to wounded warriors.

Transudative chylothorax from cirrhosis complicated by lung entrapment

A patient with long-standing cirrhosis due to hepatitis C and hepatic hydrothorax was evaluated for increasing symptoms and presence of a large right pleural effusion. Thoracentesis revealed evidence of a chylothorax with rapid reaccumulation of pleural fluid. Repeat thoracentesis with manometry identified presence of entrapped lung which complicated treatment options. This is the first case report of a hepatic chylothorax with features of entrapped lung.

Chronic Left Lower Lobe Pulmonary Infiltrates During Military Deployment

Deployment to Southwest Asia is associated with increased airborne hazards such as geologic dusts, burn pit smoke, vehicle exhaust, or air pollution. There are numerous ongoing studies to evaluate the potential effects of inhaled particulate matter on reported increases in acute and chronic respiratory symptoms. Providers need to be aware of potential causes of pulmonary disease such as acute eosinophilic pneumonia, asthma, and vocal cord dysfunction that have been associated with deployment. Other pulmonary disorders such as interstitial lung disease are infrequently reported. Not all deployment-related respiratory complaints may result from deployment airborne hazards and a broad differential should be considered. We present the case of a military member with a prolonged deployment found to have lobar infiltrates secondary to pulmonary vein stenosis from treatment for atrial fibrillation.

Radiation exposure and lung disease in today's nuclear world.

Purpose of review Ionizing radiation poses important health risks. The per capita annual dose rate has increased in the United States and there is increasing concern for the risks posed by low-dose occupational exposure among workers in nuclear industries and healthcare. Recent nuclear accidents and concern for terrorism have heightened concern for catastrophic, high-dose ionizing radiation exposure. This review will highlight recent research into the risks to lung health posed by ionizing radiation exposure and into potential treatments. Recent findings Angiotensin-converting enzyme inhibitors and some antioxidants have shown promise as mitigators, to decrease pneumonitis and fibrosis when given after exposure. Studies of survivors of nuclear catastrophes have shown increased risk for lung cancer, especially in nonsmokers. There is evidence for increased lung cancer risk in industrial radiation workers, especially those who process plutonium and may inhale radioactive particles. There does not seem to be an increased risk of lung cancer in healthcare workers who perform fluoroscopic procedures. Summary High-dose ionizing radiation exposure causes pneumonitis and fibrosis, and more research is needed to develop mitigators to improve outcomes in nuclear catastrophes. Long-term, low-dose occupational radiation may increase lung cancer risk. More research to better define this risk could lead to improved safety protocols and screening programs.