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1.  Use of the Breathlessness, Cough, and Sputum Scale (BCSS©) in Pulmonary Rehabilitation§ 
Background:
In pulmonary rehabilitation (PR) effective measures have been taken while in analyzing a patient’s intervention with the help of entry to exit evaluations. The absence of an objective and quantifiable scale are limitations of PR that allow analyzing of a patient’s self reported symptoms throughout PR. The Breathlessness, Cough and Sputum Scale (BCSS©) is used to predict patient exacerbations by evaluating common symptoms identified in the COPD population. This study used the BCSS© survey to track complex symptom changes throughout the course of PR intervention. The BCSS© tool measured the patient’s self reported symptoms in real time for each visit when patient enrolled in PR.
Methods:
Thirty-five patients with COPD from three outpatient PR centers were asked to report the severity of breathlessness, cough, and sputum prior to each PR session using the BCSS© survey.
Results:
There was a significant decrease in self reported symptoms of the mean BCSS© score from entry 4.6(± 2.9) to exit 2.3 (± 2.5), p < 0.001. The results showed variable decrease in the self reported symptoms with more PR visits. The secondary outcome showed high correlations with quality of life measures using the Pulmonary Function Status Scale (PFSS) on entry and exit to PR.
Conclusions:
The BCSS© tool is an effective means for measuring the impact of PR on improving patient tolerance and self-reported symptoms as a result of COPD. More research is needed to better assess the complex symptoms of COPD patients in PR to enhance programmatic outcomes.
doi:10.2174/1874306401307010001
PMCID: PMC3594703  PMID: 23494521
Rehabilitation; quality of life; dyspnea; cough; sputum.
2.  The Association of Septic Thrombophlebitis with Septic Pulmonary Embolism in Adults 
Background:
There have been an increasing number of pediatric reports of septic pulmonary embolism in the setting of septic thrombophlebitis adjacent to a primary infectious source.
Methods:
Retrospective review at an urban hospital. A total of five adults with a documented primary infectious source, adjacent septic thrombophlebitis and septic pulmonary embolism were identified between 2000 and 2011.
Results:
The predominant symptoms on presentation were fever and pleuritic chest pain, followed by chills and cough. S. aureus was the pathogen in 4 patients. Only one case had echocardiographic evidence of endocarditis. All patients received IV antibiotics and anticoagulation therapy. No new embolic events or central nervous system complications were noted.
Conclusions:
The triad of extrapulmonary infection, contiguous septic thrombophlebitis and septic pulmonary embolism is present in adult as well as pediatric populations. The use of systemic anticoagulation with appropriate antibiotics resulted in clinical and radiologic improvement but no significant complications.
doi:10.2174/1874306401206010014
PMCID: PMC3355351  PMID: 22611460
Septic thrombophlebitis; septic pulmonary emboli; anticoagulation.
3.  Body Mass Index, Gender, and Ethnic Variations Alter the Clinical Implications of the Epworth Sleepiness Scale in Patients with Suspected Obstructive Sleep Apnea§ 
Introduction:
The Epworth Sleepiness Scale (ESS) is often used in the evaluation of obstructive sleep apnea (OSA), though questions remain about the influence gender, ethnicity, and body morphometry have in the responses to this questionnaire. The aim of this study was to examine differences in ESS scores between various demographic groups of patients referred for polysomnography, and the relationship of these score to sleep-disordered breathing
Methods:
Nineteen hundred consecutive patients referred for polysomnographic diagnosis of OSA completed questionnaires, including demographic data and ESS. OSA was determined based on a respiratory disturbance index (RDI) ≥15 by polysomnography.
Results:
In this high risk population for OSA, the ESS was 10.7 ± 5.6. The highest ESS scores were seen in obese males; non-obese females and non-obese Caucasian males scored the lowest. ESS was weakly correlated with RDI (r = 0.17, P < 0.0001). The sensitivity of ESS for the diagnosis of OSA was 54% and the specificity was 57%. The positive (PPV) and negative (NPV) predictive values were 64% and 47%, respectively. In obese subjects, the sensitivity and specificity were 55% and 53%, compared with 47% and 63% in non-obese subjects. In obese, Hispanic males, the sensitivity, specificity, and PPV were 59%, 54%, and 84%, respectively. In non-obese, Caucasian females, the sensitivity, specificity, and NPV were 43%, 59%, and 72%.
Conclusions:
The ESS appears to be affected by many factors, including gender, ethnicity, and body morphometry. The ability of the ESS to predict OSA is modest, despite a significant correlation with the severity of OSA. The test characteristics improve significantly when applied to select populations, especially those at risk for OSA.
doi:10.2174/1874306401206010020
PMCID: PMC3367266  PMID: 22670164
Ethnicity; gender; obstructive sleep apnea; epworth sleepiness scale; screening.
4.  Asthma and COPD - The C/EBP Connection 
Asthma and chronic obstructive pulmonary disease (COPD) are the two most prominent chronic inflammatory lung diseases with increasing prevalence. Both diseases are associated with mild or severe remodeling of the airways. In this review, we postulate that the pathologies of asthma and COPD may result from inadequate responses and/or a deregulated balance of a group of cell differentiation regulating factors, the CCAAT/Enhancer Binding Proteins (C/EBPs). In addition, we will argue that the exposure to environmental factors, such as house dust mite and cigarette smoke, changes the response of C/EBPs and are different in diseased cells. These novel insights may lead to a better understanding of the etiology of the diseases and may provide new aspects for therapies.
doi:10.2174/1874306401206010001
PMCID: PMC3377872  PMID: 22715349
Asthma; COPD; airway inflammation; airway wall remodelling; CCAAT-enhancer binding proteins.
5.  Sleep Apnea in Patients with Acromegaly. Frequency, Characterization and Positive Pressure Titration 
Objectives:
to describe the frequency of sleep apnea in patients with acromegaly;to identify the proportion of candidates for treatment with positive airway pressure;to report our experience with the positive pressure titration process in acromegaly patients.
Methods:
A cross-sectional study that included the acromegaly cohort at the Centro Medico Nacional “20 de Noviembre” in Mexico City (n=44). A standard polysomnography (PSG) was carried out for each patient. A second PSG was done for purposes of CPAP titration.
Results:
A total of 35 patients were studied (80% of the cohort, 20 [57%] women). Polysomnography results showed that 34 subjects (97%, 95%CI 91-100%) had apnea hypopnea indexes (AHI) ≥ 5. No patient had central apnea. We identified 19 subjects with AHI ≥5 and Epworth ≥10, for a frequency of obstructive sleep apnea syndrome of 54% (95%CI 36-71%). A total of 31 patients (88%; 95%CI 77-99%) were deemed to be candidates for positive pressure treatment, but only 8 of them accepted CPAP. They required pressures that ranged from 10 to 18 cmH2O.
Conclusions:
Our results confirm a high prevalence of sleep apnea in patients with acromegaly, and provide evidence that the majority of those patients are candidates for treatment with positive pressure. Contrary to what has been reported, we identified no patients with central apnea.
doi:10.2174/1874306401206010028
PMCID: PMC3386499  PMID: 22754597
Acromegaly; sleep; sleep apnea; sleep-disordered breathing; growth hormone.
6.  Detection of Bordetella pertussis in Infants Suspected to have Whooping Cough 
Background:
Even with high coverage of vaccination programs, Bordetella pertussis is still reported in various countries. It causes a high rate of mortality and morbidity in infants while it could be asymptomatic in adults. At the present study, we are going to evaluate the frequency of B. pertussis among received specimens.
Methods:
This cross-sectional study was performed on 138 children under one year who were suspected to have whooping cough from October 2008 to March in 2011. Nasopharyngeal dacron and rayon swabs and sera were used for PCR and serology respectively.
Results:
The mean age of the subjects was 1.9± 0.9 months. PCR was positive in 12 cases; ELISA was in agreement with PCR results except in one case that showed the specific antibody at borderline limit.
Conclusion:
The rate of reported positive results showed that pertussis not only is still present in the community, but the number of the asymptomatic cases who are able to transmit the disease may be considerable.
doi:10.2174/1874306401206010034
PMCID: PMC3386500  PMID: 22754598
Whooping cough; B. pertussis; PCR; ELISA.
7.  Clinical and Economic Outcomes Associated with Low-Dose Fluticasone Propionate Versus Montelukast in Children with Asthma Aged 4 to 11 Years 
Objective:
Inhaled corticosteroids (ICS) are preferred first-line controller agents for adults and adolescents with asthma. There is limited effectiveness data comparing ICS to leukotriene receptor antagonists (LTRA) in children with asthma aged 4 to 11 years.
Methods:
A retrospective, matched cohort study was conducted using medical and pharmacy claims data. Asthma patients (ICD-9, 493.xx) naïve to any asthma controller therapy, and having ≥1 dispensing of fluticasone propionate 44 mcg (FP44), an ICS, or montelukast any dose (MON), an LTRA, were identified. Drug cohorts were matched (1:2) using propensity scores. Outcomes during follow-up included asthma-related ED visits, composite measure of asthma-related ED/hospital visit, asthma-related costs per month, and monthly rescue medication use. Statistical differences between cohorts were evaluated using multivariate regression models.
Results:
The final matched sample included 6,636 patients (FP44=2,212; MON=4,424). During follow-up, the FP44 cohort had a 29% significantly lower risk of an asthma-related ED visit (Hazard ratio (95% CI) =0.71 (0.52, 0.96)) compared to the MON cohort. Monthly asthma-related costs were significantly reduced on average by 36% in the FP44 compared to the MON cohort ($48 vs $75, p<0.05). Use of short-acting beta-agonists per month were similar between cohorts but monthly adjusted number of oral corticosteroid prescriptions were significantly lower in the FP44 compared to the MON cohort (0.03 vs 0.04, p<0.001).
Conclusion:
Initiation of FP44 versus MON in children with asthma aged 4 to 11 years is associated with a significant reduction in asthma-related ED visits, costs, and oral corticosteroid use.
doi:10.2174/1874306401206010037
PMCID: PMC3391652  PMID: 22787519
Asthma; pediatrics; inhaled corticosteroids; leukotriene; receptor antagonists; outcomes; costs.
8.  The Role of Surfactant in Respiratory Distress Syndrome 
The key feature of respiratory distress syndrome (RDS) is the insufficient production of surfactant in the lungs of preterm infants. As a result, researchers have looked into the possibility of surfactant replacement therapy as a means of preventing and treating RDS. We sought to identify the role of surfactant in the prevention and management of RDS, comparing the various types, doses, and modes of administration, and the recent development. A PubMed search was carried out up to March 2012 using phrases: surfactant, respiratory distress syndrome, protein-containing surfactant, protein-free surfactant, natural surfactant, animal-derived surfactant, synthetic surfactant, lucinactant, surfaxin, surfactant protein-B, surfactant protein-C.
Natural, or animal-derived, surfactant is currently the surfactant of choice in comparison to protein-free synthetic surfactant. However, it is hoped that the development of protein-containing synthetic surfactant, such as lucinactant, will rival the efficacy of natural surfactants, but without the risks of their possible side effects. Administration techniques have also been developed with nasal continuous positive airway pressure (nCPAP) and selective surfactant administration now recommended; multiple surfactant doses have also reported better outcomes. An aerosolised form of surfactant is being trialled in the hope that surfactant can be administered in a non-invasive way. Overall, the advancement, concerning the structure of surfactant and its mode of administration, offers an encouraging future in the management of RDS.
doi:10.2174/1874306401206010044
PMCID: PMC3409350  PMID: 22859930
Surfactant; RDS; natural; synthetic; protein-free; protein-containing.
9.  Precision in Diagnosing and Classifying COPD: Comparison of Historical Height with Current Height and Arm Span to Predict FEV1 
Background:
Measured reductions in lung function, as a result of COPD, use a measured current value and make comparisons to a determined ‘normal’ value arrived at using a regression equation based upon a patients height. Osteoporosis is a recognised co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and may cause excessive height loss resulting in the ‘normal’ values and disease progression being under-estimated.
Purpose:
The aim of the study was to examine the height variation in a cohort of COPD patients and controls over a 7-8 years period and evaluate its impact on estimates of lung function and hence COPD progression.
Methods:
In 1999-2002 we studied a cohort of primary care patients in Sunderland, UK with and without COPD and reexamined 104 (56 male) during 2007-2009. We calculated FEV1% predicted for actual and estimated height (armspan/1.03 and armspan/1.01 in males and females respectively).
Results:
In 1999-2002 the subjects were aged 62.6 ± 9.4 years, BMI was 26.4± 4.7 kg/m2, predicted FEV1 was 59.0 ±16.0, and mean actual height was 167.3±8.9cm. The actual height changed significantly (p<0.001) by 2cms over time in both genders. Whilst the overall classifications of the cohort did not change significantly when armspan was used to determine height and hence normal lung volume, individual cases did move to a classification of higher severity.
Conclusions:
The study suggests that current measured height may underestimate the degree of impairment of FEV1 and hence progression of COPD. The use of height, derived from armspan, may give a more accurate measure of ‘normal’ lung volumes and hence the degree of impairment.
doi:10.2174/1874306401206010054
PMCID: PMC3415627  PMID: 22896775
Chronic obstructive pulmonary disease; historical height; osteoporosis.
10.  Drug Induced Interstitial Lung Disease 
With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease.
doi:10.2174/1874306401206010063
PMCID: PMC3415629  PMID: 22896776
Lung; adverse drug reaction; drug-induced lung disease; mechanism of pulmonary toxicity; diagnosis; treatment; review.
11.  Metabolic Alkalosis in Adults with Stable Cystic Fibrosis 
Background:
The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown.
Methods:
Retrospective chart review.
Results:
Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis.
Conclusions:
Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.
doi:10.2174/1874306401206010059
PMCID: PMC3415624  PMID: 22905070
Cystic fibrosis; metabolic alkalosis.
12.  Evaluation of the Efficacy and Safety of Percutaneous Biopsy of Lung 
Introduction:
Percutanous needle biopsy of the lung (PNBL), under image guidance, has established itself as a safe and effective minimally-invasive method of obtaining a tissue diagnosis of pulmonary lesions, for selected patients with suspected pathologic processes. The purpose of this study was to evaluate the diagnostic yield and safety of percutaneous core biopsy of the lung (PCBL) without Fine Needle Aspiration Biopsy (FNAB), with specific attention to potential risk factors that may predict post-biopsy pneumothorax.
Materials and Methods:
A retrospective analysis of 75 consecutive PCBL procedures between January 2006 to March 2008 involving 72 patients with a documented pulmonary nodule or mass lesion on CT scan of Thorax. The study population included 38 males (52.8%) and 34 females (47.2%) aged 20-85 years (mean age 63.6 years). A co-axial cutting system with a 19-gauge outer needle and a 20-gauge inner automated cutting needle (Temno, Allegiance Healthcare Corporation, Ohio, USA) was used in all patients.
Results:
Lesions varied in size from 0.7cm to 10.7cm (mean maximum trans-axial diameter 3.1cm). The mean number of core biopsy samples obtained was 3.1 (range 1-5). Of the 75 PCBL procedures, 71 yielded specimens adequate for histopathologic evaluation, consistent with a technical success rate of 95%. Malignancy was detected in 48 specimens (64%) and benign diagnoses were identified in 23 specimens (31%). As mentioned, 4 specimens (5%) were nondiagnostic. The most common biopsy-induced complication was pneumothorax, occurring in 15 patients (20%), with 4 (5.3%) requiring thoracostomy tube placement.
Conclusion:
PCBL without FNAB, under CT fluoroscopy guidance, has an excellent diagnostic accuracy in obtaining a conclusive histologic diagnosis of thoracic lesions and is comparable to FNAB in terms of safety and rates of occurence of complications.
doi:10.2174/1874306401206010082
PMCID: PMC3439799  PMID: 22977650
Percutaneous biopsy of lung; non-fine needle; efficacy; safety.
13.  Unusual Bacterial Infections and the Pleura 
Rickettsiosis, Q fever, tularemia, and anthrax are all bacterial diseases that can affect the pleura. Rocky Mountain Spotted Fever (RMSF) and Mediterranean Spotted Fever (MSF) are caused by Rickettsia rickettsii and Rickettsia conorii, respectively. Pleural fluid from a patient with MSF had a neutrophil-predominant exudate. Coxiella burnetii is the causative agent of Q fever. Of the two cases described in the literature, one was an exudate with a marked eosinophilia while the other case was a transudate due to a constrictive pericarditis. Francisella tularensis is the causative agent of tularemia. Pleural fluid from three tularemia patients showed a lymphocyte predominant exudate. Bacillus anthracis is the causative agent of anthrax. Cases of inhalational anthrax from a recent bioterrorist attack evidenced the presence of a serosanguineous exudative pleural effusion. These four bacterial microorganisms should be suspected in patients presenting with a clinical history, exposure to known risk factors and an unexplained pleural effusion.
doi:10.2174/1874306401206010075
PMCID: PMC3439802  PMID: 22977649
Rickettsia; Q fever; tularemia; anthrax; pleural disease.
14.  Lung Injury in Asphyxiated Newborn Pigs Resuscitated from Cardiac Arrest - The Impact of Supplementary Oxygen, Longer Ventilation Intervals and Chest Compressions at Different Compression-to-Ventilation Ratios 
Introduction:
Non-specific lung inflammatory events caused by severe asphyxia may be intensified by the way we resuscitate the newly born. Assessing lung injury is potentially important because if alternative resuscitation approaches induces similar inflammatory responses or less lung injury. then we may choose the resuscitation approach that is most gentle, and easiest to perform and learn. We investigated the levels of lung inflammatory markers by comparing different ventilation, chest compression and inhaled oxygen fraction strategies in resuscitation of newly born pigs at cardiac arrest.
Materials and Methodology:
Progressive asphyxia in newborn pigs was induced until asystole occurred. With current resuscitation guidelines as a reference group, pigs were randomized to receive initial ventilation before chest compressions for 30s, 60s or 90s, or to compression-to-ventilation ratios 3:1or 9:3, or to resuscitation using pure oxygen or air. We analysed inflammatory markers in bronchoalveolar lavage fluid (BAL), IL8 and TNFα, and lung tissue qPCR for genes matrix metalloproteinases (MMP)2, MMP9, TNFα and ICAM-1.
Results:
BAL-levels of TNFα and IL8 tended to be higher in the 30s group compared to 60s group (p = 0.028 and p = 0.023, respectively) as was gene expression in lung tissue of ICAM-1 and MMP2 (p=0.012 and p=0.043, respectively). MMP2 expression was slightly higher in the 30s group compared to 90s group (p = 0.020). No differences were found between pigs resuscitated with C:V ratio 9:3 and 3:1 or pure oxygen versus air.
Conclusion:
Compared to current guidelines, with respect to lung injury, resuscitation with longer initial ventilation should be considered. Longer series of chest compressions did not change the lung inflammatory response, neither did the use of air instead of pure oxygen in severely asphyxiated pigs resuscitated from asystole.
doi:10.2174/1874306401206010089
PMCID: PMC3480705  PMID: 23115599
Newborn; asphyxia; lung inflammation; room air; resuscitation; BAL; MMP2; MMP9; TNFα; IL8; ICAM-1.
15.  Association Between Emphysema Score, Six-Minute Walk and Cardiopulmonary Exercise Tests in COPD 
Background:
High-resolution computed tomography (HRCT) has allowed in detection of airway wall abnormalities and emphysema, whose extent may correlate with the clinical severity of the disease in patients with chronic obstructive pulmonary disease (COPD). Six minute walk test (6MWT) and cardiopulmonary exercise test (CPET) can determine functional status.
Methods:
A study was undertaken to investigate whether the extent of emphysema in COPD patients quantitatively confirmed by HRCT scoring was associated with distance walked, inspiratory capacity (IC) changes after exercise, anaerobic threshold of cardiopulmonary exercise and the BODE index (body mass index, airflow obstruction, dyspnea, exercise performance).
Results:
Seventeen patients with COPD underwent HRCT scanning, 6MWT and CPET. The emphysema score was highly correlated to forced vital capacity (FVC) (r=-0.748, p<0.001), forced expiratory volume in 1 second (FEV1) (r=-0.615, p<0.01), IC post exercise (r=-0.663, p<0.01) and dyspnea score post exercise (r=0.609, p<0.01), but was not associated with the BODE index. The distance walked during 6MWT was inversely correlated to emphysema score (r=-0.557, p<0.05). IC before exercise was highly related to the 6MWT. The change in IC after exercise was associated with the percent decline of oxygen saturation after exercise (r=0.633, p<0.01). Severity of lung emphysema in COPD patients was inversely correlated to VO2 max (r=-0.514, p<0.05) and anaerobic threshold (r=-0.595, p<0.01) of cardiopulmonary exercise.
Conclusions:
These results suggest that COPD associated with emphysema on HRCT is characterized by more severe lung function impairment, greater exercise impairment and cardiopulmonary dysfunction.
doi:10.2174/1874306401206010104
PMCID: PMC3480708  PMID: 23115601
Chronic obstructive pulmonary disease; High-resolution computed tomography; Six-minute walk test; cardiopulmonary exercise test; Inspiratory capacity.
16.  Anxiety and Depression Symptoms in Patients with Sleep-Disordered Breathing 
Introduction:
Information concerning the frequency of anxiety and depression symptoms in patients with sleep-disordered breathing (SDB) is controversial. Hence, the objectives of this study were to: determine the frequency of anxiety and depression symptoms in patients with SDB; explore whether the frequency of anxiety and depression symptoms rises with increasing parameters of SDB severity; and investigate the factors potentially associated with anxiety and depression.
Materials and Methodology:
Data was collected from consecutive adult patients referred to the National Institute of Respiratory Diseases’ Sleep Medicine Unit from October 2008 to October 2009. SDB diagnoses were established using standard polysomnography or simplified respiratory polygraphy. All patients routinely completed the Hospital Anxiety and Depression Scale (HADS) on their first visit to the Sleep Medicine Unit.
Results:
382 patients with SDB were included. Mean age was 50.8±13.6 years, 62% were male. Anxiety symptoms were acknowledged by 71 patients (18.5%), while 29 (7.6%) had depression symptoms, and 116 (30.4%) had symptoms of anxiety plus depression. Patients who reported anxiety and depression symptoms scored higher on the Epworth Sleepiness Scale (ESS, 16±7) than those with no symptoms (11±6) (p<0.0001). Patients with symptoms of anxiety plus depression also had higher BMIs (36 ± 8 K/m2) than patients with SDB without anxiety or depression. No other differences were observed, not even with respect to the parameters of the severity of their SDB.
Conclusions:
Our results support the recommendation that due to their high frequency and potential importance for long-term adherence to CPAP, anxiety and depression symptoms should be included in the routine evaluation of all adults with SDB.
doi:10.2174/1874306401206010097
PMCID: PMC3480709  PMID: 23115600
Anxiety; depression; sleep-disordered breathing; sleep apnea; mood disorders.
17.  Expiratory Flow Limitation in Obstructive Sleep Apnea and COPD: A Quantitative Method to Detect Pattern Differences Using the Negative Expiratory Pressure Technique 
Background:
Expiratory flow limitation (EFL), determined by the negative expiratory pressure (NEP) technique, can exhibit overlapping patterns in COPD, obstructive sleep apnea (OSA) and non-OSA obesity. We assessed the ability of a quantitative method to assess EFL to discriminate COPD from obese and OSA patients during NEP (-2 to -3 cm H2O) testing.
Methods:
EFL was quantified by measuring the area under the preceding control tidal breath (Vt) subtended by the NEP curve (%AUC). To quantify mean lost flow, the ratio of %AUC to percentage of control Vt over which EFL occurred (%EFL) (= %AUC/%EFL) was computed. Percent EFL, %AUC, and %AUC/%EFL was compared in 42 patients with COPD, 28 obese subjects without OSA, 50 with OSA (26 mild-moderate, 24 severe) and 19 control subjects, in seated and supine postures.
Results:
All patients exhibited %EFL values significantly higher than control subjects, corrected for age and gender (ANOVA). All but the COPD group exhibited higher %EFL while supine, but not %AUC or %AUC/%EFL. Amongst seated subjects, %EFL was highest in COPD, and amongst supine groups, it was greatest in OSA and COPD. %AUC/%EFL was significantly higher in mild-moderate OSA than in COPD only while seated. %AUC or %AUC/%EFL did not discriminate amongst other cohorts in either posture.
Conclusions:
Computation of %EFL helps distinguish EFL in COPD, obese and OSA patients from those of control subjects. Computation of %AUC and %AUC/%EFL is useful in determining the magnitude of extrathoracic FL in individuals with obesity and OSA, but does not distinguish between cohorts.
doi:10.2174/1874306401206010111
PMCID: PMC3496931  PMID: 23166569
Negative expiratory pressure; sleep apnea; COPD.
18.  Extra-Esophageal Manifestations of Gastroesophageal Reflux Disease: Controversies Between Epidemiology and Clicnic 
Gastroesophageal reflux disease (GERD) is widely associated with asthma, chronic cough, and laryngitis. Many studies have focused on acidic reflux; however, acid is just one of many factors that can cause pulmonary injury. The discrepancy between the high frequency of GERD in asthmatic patients and the ineffective reflux therapy outcomes in these patients suggests that GERD may cause injury through other mechanisms, such as pepsinogen, pepsin, bile salts, or other components of reflux materials, instead of the acid. Research using appropriate and innovative methodologies to investigate these potential inflammatory agents in patients with GERD is required to determine the underlying factors associated with pulmonary disorders in these patients.
doi:10.2174/1874306401206010121
PMCID: PMC3499735  PMID: 23166570
Gastroesophageal reflux disease; respiratory; asthma; cough; epidemiology.
19.  Nitric Oxide Metabolites as Biomarkers for Influenza-Like Acute Respiratory Infections Presenting to the Emergency Room 
Aims:
Nitric oxide (NO) is increased in the respiratory tract in pulmonary infections. The aim was to determine whether nasal wash NO metabolites could serve as biomarkers of viral pathogen and disease severity in children with influenza-like illness (ILI) presenting to the emergency department (ED) during the 2009 influenza A H1N1 pandemic.
Methods:
Children ≤18 years old presenting to the ED with ILI were eligible. Nasal wash specimens were tested for NO metabolites, nitrate and nitrite, by HPLC and for respiratory viruses by real-time PCR.
Results:
Eighty-nine patients with ILI were prospectively enrolled during Oct-Dec, 2009. In the entire cohort, nasal wash nitrite was low to undetectable (interquartile range [IQR], 0 - 2 μM), while median nitrate was 3.4 μM (IQR 0-8.6). Rhinovirus (23%), respiratory syncytial virus (RSV) (20%), novel H1N1 (19%), and adenovirus (11%) were the most common viruses found. Children with RSV subtype B-associated ILI had higher nitrate compared to all other viruses combined (P=0.002).
Conclusion:
Concentration of NO-derived nitrate in nasal secretions in children in the ED is suggestive of viral pathogen causative for ILI, and thus might be of clinical utility. Predictive potential of this putative biomarker for ILI needs further evaluation in sicker patients in a prospective manner.
doi:10.2174/1874306401206010127
PMCID: PMC3499797  PMID: 23166571
Acute respiratory infections; emergency department; nitrate; Novel H1N1; pediatrics; RSV.
20.  Reduction of Raf Kinase Inhibitor Protein Expression is Associated with Lymph Node Metastasis in Resectable Non-small Cell Lung Cancer  
Introduction:
Raf kinase inhibitor protein (RKIP) had been identified as one of prognostic indictor in various malignant diseases. Association of RKIP expression and the clinical-pathological features were not investigated in patients with resectable non-small cell lung cancer (NSCLC).
Materials and Methodology:
159 sectioned samples from surgical NSCLC patients were investigated by immunohistochemistry in order to reveal the associations between RKIP expression and clinical-pathologic features.
Results:
Statistically, Lower RKIP expression level was found in the group with higher N stage (P<0.01) and higher TNM stage (P<0.05). No significant correlation was observed between RKIP expressions and histologic type (P>0.05) and tumor size (P>0.05).
Conclusions:
Down expression level of RKIP was found relating to lymph node metastasis in resectable NSCLC patients in this study.
doi:10.2174/1874306401206010135
PMCID: PMC3520034  PMID: 23248718
Raf kinase inhibitor protein; non-small cell lung cancer; lymph node metastasis.
21.  CT Densitometry as a Predictor of Pulmonary Function in Lung Cancer Patients 
Purpose:
Preoperative pulmonary assessment is undertaken in patients with resectable lung cancer to identify those at increased risk of perioperative complications. Guidelines from the American College of Chest Physicians indicate that if the FEV1 and DLCO are ≥60% of predicted, patients are suitable for resection without further evaluation.
The aim of our study is to determine if quantitative measures of lung volume and density obtained from pre-operative CT scans correlate with pulmonary function tests. This may allow us to predict pulmonary function in patients with lung cancer and identify patients who would tolerate surgical resection.
Materials and Methods:
Patients were identified retrospectively from the lung cancer database of a tertiary hospital. Image segmentation software was utilized to estimate total lung volume, normal lung volume (values -500 HU to -910 HU), emphysematous volume (values less than -910 HU), and mean lung density from pre-operative CT studies for each patient and these values were compared to contemporaneous pulmonary function tests.
Results:
A total of 77 patients were enrolled. FEV1 was found to correlate significantly with the mean lung density (r=.762, p<.001) and the volume of emphysema (r= -.678, p<.001). DLCO correlated significantly with the mean lung density (r =.648, p<.001) and the volume of emphysematous lung (r= -.535, p<.001).
Conclusion:
The results of this study suggest that both FEV1 and DLCO correlate significantly with volume of emphysema and mean lung density. We now plan to prospectively compare these CT parameters with measures of good and poor outcome postoperatively to identify CT measures that may predict surgical outcome preoperatively
doi:10.2174/1874306401206010139
PMCID: PMC3527876  PMID: 23264834
Computed tomography; lung density; pulmonary function
22.  Aclidinium Bromide: Clinical Benefit in Patients with Moderate to Severe COPD 
Background and Aim:
Long-acting bronchodilators are the mainstay of pharmacological treatment for patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the safety and efficacy of inhaled aclidinium bromide, a novel long-acting anticholinergic bronchodilator, for the treatment of COPD.
Method:
This systematic review explored the efficacy and safety of aclidinium bromide in comparison with placebo and other long-acting bronchodilators for treatment of moderate to severe COPD. Randomised controlled trials were identified through systematic searches of different databases of published trials.
Results:
Ten trials (3.922 participants) were included. Aclidinium bromide appears to be a safe and well-tolerated long-acting anti-cholinergic bronchodilator with a relatively fast onset of action. Compared with other long-acting bronchodilators, including tiotropium bromide, aclidinium bromide leads to at least similar clinically important improvements in level of FEV1, health status, use of rescue medication, and day-time dyspnea scores in patients suffering from moderate to severe COPD. With twice-daily dosing, aclidinium bromide may have clinically important effect on night-time symptom scores in COPD patients, but further studies are needed in order to permit valid conclusions with regard to this point. The effect of aclidinium bromide on exercise tolerance, as assessed by exercise endurance time, and dynamic hyperinflation in patients with moderate to severe COPD seems to be at least comparable to other long-acting bronchodilators, incl. tiotropium bromide and indacaterol. Aclidinium bromide might reduce the rate of exacerbations in COPD patients, but conclusions must await further long-term controlled trials.
Conclusion:
Aclidinium bromide has effects on relevant COPD outcome measures, including level of FEV1, similar to other long-acting bronchodilators, and therefore seems to have the potential for a significant role in the future management of moderate to severe COPD.
doi:10.2174/1874306401206010150
PMCID: PMC3527890  PMID: 23264836
COPD; aclidinium; long-acting antimuscarinic agents; long-acting; bronchodilators.
23.  Chronic Candidal Bronchitis: A Consecutive Series 
Background:
Persistent Candida from fungal cultures of respiratory secretions are often ignored and not treated due to assumptions concerning benign colonization.
Objectives:
To determine the clinical course of patients with chronic sputum and fungi on culture, including response to antifungal treatment.
Methods:
All patients seen at a single long term acute care hospital (LTAC) between May 2009 and September 2010 with at least two months of daily sputum and fungus on more than one sputum culture were identified. LTAC, inpatient, and outpatient records through June 2011 were reviewed to assess clinical features and response to therapy or to cessation of therapy.
Results:
Eleven patients were identified, having sputum duration of 5 months to 28 years, and respiratory cultures growing Candida species. Fungi included C albicans (8 patients), C glabrata (2), C krusei (2), C tropicalis (1), C parapsilosis (1), Aspergillus fumigatus (1), Aspergillus terreus (1), and Scedosporium (1), the latter 3 in conjunction with Candida species. All had abnormal chest CT scans, often with bronchiectasis and sometimes atelectasis or consolidation, and ten of 11 patients were on chronic steroids (inhaled and/or systemic). Antifungal therapy, mostly oral voriconazole and nebulized amphotericin, led to improved respiratory symptoms and sputum within 3 weeks in 10 of 10 treated patients. Lack of antifungal therapy or early cessation of treatment was associated with progressive or recurrent symptoms and death of one patient.
Conclusions:
This case series suggests that chronic candidal bronchitis is associated with significant morbidity and responds well to treatment. Such patients may benefit from extended antifungal therapy. Guidelines for the treatment of Candida in pulmonary secretions should be reevaluated.
doi:10.2174/1874306401206010145
PMCID: PMC3527895  PMID: 23264835
Antifungal; amphotericin; bronchiectasis; Candida; chronic bronchitis; prednisone; voriconazole
24.  Classification of Centrilobular Emphysema Based on CT-Pathologic Correlations 
Introduction:
Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular distribution on high-resolution computed tomography. The LAA often exhibit a variety of shape or sharpness of border. This study was performed to elucidate the relationship between morphological features of LAA and pathological findings in CLE.
Materials and Methods:
The inflated-fixed lungs from 50 patients with CLE (42 males, 8 females; 14 operated, 36 autopsied) were examined by a method of CT-pathologic correlations that consisted of three steps. The first, CT images of the sliced lungs of the inflated-fixed lung specimens were examined on the shape and the peripheral border of each LAA. The second, the sliced lungs were radiographed in contact with high magnification. The third, the surface of the sliced lungs was observed by using stereomicroscopy. The views at low magnification of stereomicroscope were compared with the radiographs and the CT images of the same sample.
Results:
Using CT-pathologic correlations, LAAs of CLE were classified into three types as follows; round or oval shape with well-defined border (Type A), polygonal or irregular shape with ill-defined border and less than 5 mm in diameter (Type B), and irregular shape with ill-defined border and 5 mm or over in diameter (Type C). Type A, Type B and Type C LAA were mainly related to dilatation of bronchioles, destruction of proximal part of alveolar ducts, and destruction of distal part of alveolar ducts, respectively. Type A, Type B and Type C were dominant LAA in 5 (10%), 29 (58%) and 12 (24%) patients, respectively. However, remained 4 patients (8%) did not show dominant LAA type.
Conclusion:
Morphological features of LAA in CLE may depend on dilatation or destruction of certain parts of the secondary lobule. Type B LAA was the commonest type in CLE.
doi:10.2174/1874306401206010155
PMCID: PMC3527991  PMID: 23264837
Low attenuation area; computed tomography; radiograph; stereomicroscopy.
25.  Biomarkers of Fibroproliferative Healing in Fibrosing Idiopathic Interstitial Pneumonias 
Aims:
The main feature of fibrosing idiopathic interstitial pneumonias (fIIPs) is the fibroproliferative potential of underlying pathogenetic process. We hypothesize that the concentration of potential markers of fibroproliferative healing, PAR-2, TGF-β1, TNF-α and IL-4Rα in bronchoalveolar lavage fluid (BALF) differ in patients with fIIPs compared to controls (C).
Patients and Methods:
10 patients with fIIPs and 9 controls (C) were included to the study.
Concentrations of CD124 (IL4Rα), PAR-2, TGF-β1 and TNF-α in BALF were determined using the ELISA method.
Results:
We observed higher concentrations of IL4Rα (fIIPS 1499.4 pg/ml vs C 255.5 pg/ml; p < 0.05), PAR-2 (fIIPS 1807.9 pg/ml vs C 421.0 pg/ml; p < 0.05) and TGF-β1(fIIPS 283.0 pg/ml vs C 197.1 pg/ml; p < 0.01) in BALF in fIIPs versus C. The values of TNF-a in BALF did not differ significantly in fIIPs compared to controls. The ratios also showed differences in fIIPS and C: IL4Rα/TGF-β1 (fIIPS 6.19 vs C 0.68; p = 0.0143); TNF-α/IL4Rα (fIIPS 0.84 vs C 7.93; p = 0.043); TGF-β1/TNF-α (fIIPS 0.21 vs C 0.16; p = 0.0179) and protein/PAR-2 (fIIPS 0.06 vs C 0.28; p = 0.0033).
Conclusions:
We found that PAR-2, TGF-β1 and IL-4Rα are significantly up-regulated in the BALF of fIIPs compared to controls, therefore we suppose they could become biomarkers of fibroproliferative healing.
doi:10.2174/1874306401206010160
PMCID: PMC3551240  PMID: 23346263
Idiopathic interstitial pneumonias; fibroproliferative healing; biomarkers; bronchoalveolar lavage fluid; PAR-2; TGF-beta; IL4R.

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