Julie Biller

Utility of exhaled breath condensates in chronic obstructive pulmonary disease: a critical review

Purpose of review Evaluation of the utility of exhaled breath condensates in chronic obstructive pulmonary disease. Recent findings Exhaled breath condensates have recently been introduced as a simple, noninvasive method of sampling respiratory fluid in inflammatory lung disorders, including chronic obstructive pulmonary disease. Increases in condensate concentrations of at least 12 markers of inflammation have been reported in these disorders. Furthermore, condensate pH appears to be decreased in both chronic obstructive lung disease and bronchial asthma. This has been referred to as acidopnea and could reflect airway acidification by inflammatory cells. Although safer and more convenient than bronchoalveolar lavage, interpretation of condensate data is complicated by uncertainty regarding the source of condensate solutes and by variable dilution of respiratory droplets from condensed water vapor, which represents more than 99.9% of condensate volumes. This dilution can be estimated from the dilution of plasma constituents such as urea or electrolytes. Because the principal buffer in condensate is NH4+, much of which is derived from bacterial degradation of urea in the mouth, condensate pH measurements may not provide accurate estimates of airway pH. Nevertheless, acidification of condensate may be indicative of gastroesophageal reflux, which frequently occurs in obstructive lung diseases and may contribute to cough and bronchospasm. Summary It is too early to tell how useful condensate studies will be to pulmonary investigators and clinicians. Realization of the enormous potential of this approach will require a thorough understanding of the manner in which these solutions are generated and how they should be analyzed.

Restrictive Lung Disease is an Independent Predictor of Exercise Intolerance in the Adult with Congenital Heart Disease

BACKGROUND/OBJECTIVES Following repair of congenital heart disease (CHD), adult patients are at risk for reduced exercise capacity. Restrictive lung disease (RLD) may contribute to reduced exercise capacity in this population. The aim of this study was to determine the prevalence of RLD and its impact on exercise tolerance in the adult with CHD. METHODS One hundred consecutive adult patients with CHD, who underwent routine cardiopulmonary exercise testing with spirometry, were evaluated. Clinical data were obtained by retrospective chart review. RESULTS Patients from 10 major diagnostic groups were identified. The median age for the cohort was 31 years (range 18-63) and included 43 males and 57 females. Most patients, 79%, had at least one previous surgical procedure. Based on spirometry and flow/volume loops, 50 patients were classified as normal pulmonary function, 44 patients had patterns suggestive of RLD, 4 suggestive of mixed (obstructive and restrictive), and 2 indeterminate. Risk factors associated with RLD include history of multiple thoracotomies (odds ratio = 9.01, P =.05) and history of atrial arrhythmias (odd ratio = 4.25, P =.05). Overall, 56% of the patients had abnormal exercise capacity. Spirometry suggestive of RLD was a significant risk factor for decreased exercise capacity (odds ratio = 3.65, P =.03). Patients with spirometry suggesting RLD also had lower exercise duration (P =.004) and a higher New York Heart Association Functional Class (P =.02). History of previous surgery and decreased heart rate reserve were also significant risk factors for decreased exercise capacity. CONCLUSION Abnormal spirometry suggestive of RLD is common in the adult with CHD and is a significant risk factor for decreased exercise tolerance in this population. Further studies are needed to evaluate the relationship between RLD and exercise intolerance and its relationship to mortality in the adult with CHD.

Anemia in Cystic Fibrosis: Incidence, Mechanisms, and Association With Pulmonary Function and Vitamin Deficiency

BACKGROUND Anemia is associated with increased morbidity and mortality in many chronic diseases. Little is known about anemia in cystic fibrosis (CF). Because the majority of patients with CF die of lung disease, the objective of this study was to identify the frequency, severity, and mechanisms of anemia in CF and to determine if there was an association between anemia and poor lung function in these patients. Vitamin deficiency was used to assess the association of malabsorption and anemia. METHODS Charts of 218 CF patients (ages >1 month to 61 years) were reviewed. Information extracted included medical history, complete blood counts, iron studies, pulmonary function tests, vitamin levels, serum creatinine levels, and medications. RESULTS As patients aged, anemia increased from 12% in those < 16 to 58.3% > or = age 40. Anemic patients had poorer lung function than nonanemic patients. Mean forced expiratory volume (FEV(1)) and forced vital capacity (FVC) were 51.6% (SEM +/- 10.3) and 69.7% (SEM +/- 9.3) in anemic and 82.5% (SEM +/- 9.2) and 95% (SEM +/- 8.3) in nonanemic patients, respectively (P < .001). Of vitamin-deficient patients, 90% were anemic whereas only 59.5% of nonvitamin-deficient patients were anemic (P = .02). Complete iron studies were only available in 17 of 48 anemic patients and 11 were diagnosed with iron deficiency. CONCLUSIONS Anemia in CF is associated with poor lung function and vitamin deficiency. Although anemia was often incompletely evaluated, iron deficiency was common. Recognition and complete evaluation of anemia might be important for continued improvement of care in CF.

Response of the lungs to aspiration

Aspiration of acid from the stomach and water from the mouth can cause significant lung injury. Animal experiments suggest that acid entering the lungs is normally neutralized by bicarbonate derived from the plasma. It is hypothesized that this process may be impaired in patients with cystic fibrosis and that some of the airway injury that they experience may be related to this defect. This disease is characterized by abnormalities in the cystic fibrosis transmembrane conductance regulator, which normally conducts bicarbonate and chloride exchange. Evidence is discussed regarding the role of water channels (aquaporins) in transporting water from the airspaces into the vasculature.

FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: A diagnostic pitfall

BACKGROUND As extra-cranial metastasis of glioblastoma multiforme (GBM) is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB) cytology. CASE PRESENTATION We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP) immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. CONCLUSION Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

Exhaled breath condensates: a potential novel technique for detecting aspiration

There is an urgent need for diagnostic procedures that can detect aspiration of oral and gastrointestinal (GI) secretions into the respiratory tract. Current approaches are limited by poor sensitivity and specificity. These techniques include (1) adding indicators to feedings; (2) recovery of lipid-filled macrophages in respiratory secretions; (3) measurement of changes in the pH of the upper GI and respiratory tracts; (4) endoscopic visualization of reflux events; and (5) measurement of increased glucose concentrations in respiratory secretions. Ideally, specific markers from various sites in the oral and GI tracts might be discovered in respiratory secretions, but conventional bronchoalveolar lavage for sampling respiratory secretions is not practical and involves some risk. Noninvasive measurements of indicators in the exhaled breath condensates could be used to detect aspiration, but a number of theoretical and practical aspects of such studies must be considered before this approach can be applied to the problem of aspiration.

Effectiveness of a Cognitive Behavioral Intervention for Young Adults with Cystic Fibrosis

This study examined the effectiveness of a cognitive behavioral intervention for young adults with cystic fibrosis (CF). Four young adults were referred for the therapy by medical staff because of perceived problems with anxiety, anger, or coping. Treatment impact was assessed on measures of anxiety, anger, perceptions of functional disability, and coping. A multiple baseline design across subjects was used. Overall, the impact of the cognitive behavioral intervention for young adults with CF was mixed. If participants had elevated baseline scores on anxiety, anger, or perceived functional disability, then some improvement was shown. However, only one participant had elevated baseline anxiety and anger scores, while two had higher functional disability scores. For coping, only one participant clearly displayed a greater use of approach relative to avoidance coping by the end of treatment. Results are discussed in terms of treatment implications, assessment, and coping issues.

Inhaled antibiotics: the new era of personalized medicine?

Purpose of review Treatment options for individuals with cystic fibrosis (CF) have improved survival significantly over the past two decades. One important treatment modality is inhaled antibiotics to treat chronic infection of the airways. This review includes those antibiotics that are currently in use, those that are in clinical trials. It also includes review of nonantibiotic antimicrobials, a growing area of investigation in CF. Recent findings There are currently three inhaled antibiotics that are approved for use in patients with cystic fibrosis: tobramycin, aztreonam, and colistimethate. Tobramycin and colistimethate now are available as solution and new dry powder formulations, which are helping the treatment burden which has increased in CF. New antibiotics are in trial, although recently two did not meet primary outcomes in large clinical trials. Of particular interest is the development of nonantibiotic antimicrobials, which may allow treatment of intrinsically antibiotic resistant organisms. Summary Inhaled antibiotics remain an important treatment option in cystic fibrosis due to chronic airway infection as a hallmark of the disease. Although there are now multiple options for treatment, improvements in this treatment class are needed to treat intrinsically resistant organisms. New formulation of antibiotics and nonantibiotic antimicrobials are being evaluated to add to our armamentarium.