Effects of Osteopathic Manual Therapy on Hyperinflation in Patients with Chronic Obstructive Pulmonary Disease: A Randomized Cross-Over Study.

Osteopathic manual therapy (OMT) may reduce hyperinflation in patients with chronic obstructive pulmonary disease (COPD) by improving breathing mechanics. The aim of the study was to evaluate the immediate effects of OMT on hyperinflation in stable COPD patients with forced expired volume in 1 s (FEV1) <50% predicted. Nineteen COPD patients of the median age 68 (IQR 63-72) years and the median FEV1 39.8 (IQR 33.4-46.6) % predicted were enrolled into the study. For the first session, patients were randomly assigned to either OMT or sham therapy. During the second session, the two groups of patients were crossed over. Pulmonary function and dyspnea were compared before and after both procedures. Neither pulmonary function nor dyspnea differed significantly before and after OMT or sham procedures. However, 36.7% and 47.4% patients achieved the minimally important difference for residual volume (RV) reduction after both OMT and sham therapy, respectively. Responders to OMT had a greater median (IQR) baseline sense of dyspnea compared to non-responders, assessed on a visual analog scale, of 7.0 (4.5-7.0) vs. 3.0 (0.0-5.0), p = 0.040, respectively. Although OMT did not have an immediate effect on hyperinflation or dyspnea, a subgroup experienced a reduction in RV following OMT and sham therapy. Future studies are needed to identify the characteristics of responders.

Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

Acute Response to Cigarette Smoking Assessed in Exhaled Breath Condensate in Patients with Chronic Obstructive Pulmonary Disease and Healthy Smokers.

The effect of acute exposure to cigarette smoke (CS) on the respiratory system has been less extensively studied than the long term effects of smoking. The aim of the present study was to evaluate the acute response to CS in smokers suffering from chronic obstructive pulmonary disease (COPD) and in healthy smokers. Nineteen stable COPD patients and 19 young healthy smokers were enrolled. Tumor necrosis factor alpha (TNF-α), IL-1ß, and malondialdehyde (MDA) were measured in exhaled breath condensate (EBC) before and 60 min after smoking a cigarette. When pre- and post-CS levels of the evaluated biomarkers were compared, no differences were found in either group. However, the post-CS MDA was significantly greater in healthy smokers than that in COPD patients; 20.41 vs. 16.81 nmol/L, p = 0.01, respectively. Post-CS TNF-α correlated inversely with FEV1/FVC in healthy smokers. We conclude that CS does not acutely increase the EBC concentration of the inflammatory markers either in COPD patients or healthy smokers. The short term CS-induced oxidative stress is higher in young smokers than in COPD patients, which what may indicate a higher susceptibility to CS content of the former.

Exacerbations of Chronic Obstructive Pulmonary Disease and Quality of Life of Patients.

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the most important factors which influence the course of disease and quality of life in COPD patients. The aim of the study was to assess the exacerbation frequency in COPD patients in relation to COPD severity and to evaluate the impact of the number of exacerbations on quality of life. The study included 445 COPD patients in all four progressive stages of the disease according to GOLD classification. The patients recorded exacerbations in diaries. Spirometry, St. George's Respiratory Questionnaire, and dyspnea score were assessed at baseline and after 12 and 24 months from enrollment. After 24 months, 261 diaries were returned. The mean number of exacerbations per year in the sequential GOLD 1-4 stages of COPD was as follows: 1.3 ± 2.1, 1.4 ± 2.0, 1.7 ± 1.8, and 3.4 ± 4.5. A statistical difference in the exacerbation frequency was noted for GOLD 4 and the remaining groups. A significant negative correlation was found between the number of exacerbations and functional status for GOLD 2 and 3 stages. We conclude that the number of exacerbations is the highest in the most severe stage of the disease. The quality of life of patients with moderate and severe COPD correlates negatively with the number of exacerbations.

Causes of Chronic Cough in Non-smoking Patients.

Chronic cough is a common medical problem. The aim of the study was to analyze chronic cough causes in non-smoking patients and to search for demographic factors associated with different cough reasons. The etiology of cough was determined by medical history, diagnostic tests and response to specific treatment. Patients with significant abnormalities in the chest radiograph or spirometry were not included. The study included 131 non-smoking patients; median age 54 years, 77 % female. The most frequent causes of cough were gastroesophageal reflux disease (GERD) (62 %) and upper airway cough syndrome (UACS) (46 %). Cough variant asthma and non-asthmatic eosinophilic bronchitis (NAEB) were diagnosed in 32 (25 %) and 19 (15 %) patients, respectively. Other cough causes were found in 27 patients (21 %). Asthma was a significantly more common cause of chronic cough in women than in men (31 % vs. 3 %, p = 0.005). A reverse relationship was demonstrated for UACS (39 % vs. 67 %, p = 0.01). Patients with chronic cough aged >50 yrs were more likely to be diagnosed with less common cough causes. In conclusion, the most common chronic cough reasons are GERD and UACS. Asthma-related cough is diagnosed more frequently in females, while UACS-related cough is more frequent in males.

Diagnostic accuracy of contrast-enhanced computed tomography and positron emission tomography with 18-FDG in identifying malignant solitary pulmonary nodules.

Contrast-enhanced computed tomography (CECT) and positron emission tomography with 18-FDG (FDG-PET/CT) are used to identify malignant solitary pulmonary nodules. The aim of the study was to evaluate the accuracy of CECT and FDG-PET/CT in diagnosing the etiology of solitary pulmonary nodule (SPN). Eighty patients with newly diagnosed SPN >8 mm were enrolled. The patients were scheduled for either or both, CECT and FDG-PET/CT. The nature of SPN (malignant or benign) was determined either by its pathological examination or radiological criteria. In 71 patients, the etiology of SPN was established and these patients were included in the final analysis. The median SPN diameter in these patients was 13 mm (range 8-30 mm). Twenty-two nodules (31%) were malignant, whereas 49 nodules were benign. FDG-PET/CT was performed in 40 patients, and CECT in 39 subjects. Diagnostic accuracy of CECT was 0.58 (95% confidence interval [CI] 0.41-0.74). The optimal cutoff level discriminating between malignant and benign SPN was an enhancement value of 19 Hounsfield units, for which the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CECT were 100%, 37%, 32%, and 100%, respectively. Diagnostic accuracy of FDG-PET/CT reached 0.9 (95% CI 0.76-0.9). The optimal cutoff level for FDG-PET/CT was maximal standardized uptake value (SUV max) 2.1. At this point, the sensitivity, specificity, PPV, and NPV were 77%, 92%, 83%, and 89%, respectively. The diagnostic accuracy of FDG-PET/CT is higher than that of CECT. The advantage of CECT is its high sensitivity and negative predictive value.

Variability of Transcutaneous Oxygen and Carbon Dioxide Pressure Measurements Associated with Sensor Location.

Transcutaneous measurement of oxygen and carbon dioxide pressure (PtcO2 and PtcCO2) is useful in gas exchange monitoring. However, the relationship between PtcO2, pulse oximetry (SaO2) and arterial blood gases (ABG) is unclear. The aim of the present study was to compare PtcO2 and PtcCO2 with SaO2 and ABG, to evaluate the effect of sensor location on the results and stability of PtcO2 and PtcCO2, and to assess the impact of body composition on PtcO2 and PtcCO2. PtcO2 and PtcCO2 were measured in 20 healthy volunteers at three locations: right second intercostal space, lateral surface of the abdomen, and the inner surface of the left arm. The results were recorded 10, 15, and 20 min after sensor fixation and compared with SaO2 and ABG measured 20 min after electrode placement on the chest. Body composition was evaluated by bioimpedance. The findings were that PtcO2 was stable on the chest; but on the arm and abdomen it increased and reached maximum at 20 min. Transcutaneous PCO2 stabilized at 10 min in all the three locations. No significant correlations between PtcO2 and SaO2 or PaO2 were found. Transcutaneous PCO2 correlated with PaCO2. Both PtcO2 and PtcCO2 were not influenced by body composition. We conclude that the value of PtcO2 in monitoring of blood oxygenation was not unequivocally confirmed; PtcCO2 reliably reflects PaCO2, irrespective of sensor location. Body composition does not affect PtcO2 and PtcCO2.

Relationship between airway wall thickness assessed by high-resolution computed tomography and lung function in patients with asthma and chronic obstructive pulmonary disease.

Airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) results in thickening of bronchial walls and may affect lung function. In the present study we set out to evaluate the relationship between small airway wall thickness and the lung function parameters in patients with asthma and COPD. The study was performed in 10 patients with asthma (4M/6F, the mean age 37+/-13 yr) and 12 patients with COPD (7M/5F, the mean age 57+/-9 yr) with stable, mild to moderate disease. The study group characteristics were based on clinical assessment and lung function testing (spirometry, body plethysmography, methacholine challenge test). All patients underwent chest high resolution computerized tomography with small bronchi (external diameter 1-5 mm) cross section measurements at five selected lung levels. The following parameters were measured in end-inspiratory scans: external (D) and internal (L) diameters, wall area (WA), percentage of the wall area (WA%), wall thickness (WT), and WT/D ratio (BWT). We found no significant correlations between airway wall thickness and spirometric parameters in either group. In the asthma group, the relationships between WA% and BWT, on the one side, and postbronchodilator residual volume, on the other, were noted (r=0.72; P<0.05 and r=0.72; P<0.05, respectively). In the COPD group, WA% related with airway resistance (r=0.72; P<0.05). The correlations between WA% and PC(20) (r=-0.61; P<0.05) and BWT and PC(20) (r=-0.72; P<0.05) were found in the COPD group. There was also a relationship between WA% and airway resistance (Raw) (r=0.72; P<0.05) and BWT and Raw (r=0.45; P=0.1). The number of pack-years correlated with WA and WT in COPD patients. In conclusion, the study shows that the thickening of airway wall in asthma is reflected by an increase in the indices of air trapping and in COPD this thickening results in a higher airway resistance and responsiveness. In COPD, the thickening of airway wall also is related to exposure to tobacco smoke.

Relationship between airway inflammation and remodeling in patients with asthma and chronic obstructive pulmonary disease.

UNLABELLED: Despite a number of important differences in the pathogenesis, course and prognosis of asthma and chronic obstructive pulmonary disease (COPD), these two entities also have common features with airway inflammation being one of them. Airway remodeling is a characteristic feature of asthma, but data on the bronchial wall thickening in COPD patients are still scarce. AIM: To assess the relation between the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and thickness of bronchial walls assessed by high resolution computed tomography (HRCT) in asthma and COPD patients. MATERIAL AND METHODS: The study was conducted in 9 patients with mild-to-moderate asthma (M/F 4/5, mean age 35 +/- 10 years) and 11 patients with mild-to-moderate COPD (M/F 7/4, mean age 57 +/- 9 years). In all subjects lung function tests and HRCT scanning of the chest were performed. External (D) and internal (L) diameters of the airways were assessed at five selected lung levels. The lumen area (A(L)), wall area (WA), wall thickness (WT) and bronchial wall thickness (WT/D ratio) were calculated. Eight patients with asthma and 8 patients with COPD underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). Total and differential cell counts were assessed in the BAL fluid. RESULTS: Mean FEV(1)% pred was 80 +/- 19%, and 73 +/- 20% in asthma and COPD patients, respectively (NS). No significant differences in the total and differential cell counts in BALF were found in patients with asthma and COPD. There were no significant differences in the airway diameter or airway wall thickness. The mean inner airway diameter was 1.4 +/- 0.3 and 1.2 +/- 0.3 mm and the mean lumen area was 1.8 +/- 0.7 and 1.6 +/- 0.7 mm(2) in asthma and COPD, respectively (NS). Negative correlations between the eosinophil count in BALF and inner airway diameter (r=-0.7, P<0.05) and lumen area (r=-0.7, P<0.05) were found in asthmatics. There was no significant relationship between the BALF cell count and airway wall thickness in COPD patients. - CONCLUSIONS: In mild-to-moderate asthma and COPD the airway diameter and thickness are similar. In asthmatics, the airway diameter might be associated with eosinophil count in BAL fluid.

Diagnostic utility of pleural fluid and serum markers in differentiation between malignant and non-malignant pleural effusions.

STUDY OBJECTIVE: To evaluate the diagnostic value of four different tumor markers: cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron specific enolase (NSE) in patients with malignant and non-malignant pleural effusion. MATERIAL AND METHODS: One hundred and two patients with pleural effusion treated in the University Hospital in Warsaw between 2001 and 2003 were studied. They underwent an extensive, diagnostic work-up in order to determine the pleural effusion etiology. Patients with known pleural fluid etiology were labeled as the study group and submitted for further analysis. Pleural fluid and serum samples for CA-125, CEA, CYFRA 21-1 and NSE measurements were collected during the first thoracentesis, centrifuged, and frozen until further use. Pleural fluid and serum concentration of tumor markers were assessed by electrochemiluminescence methods using commercial kits. RESULTS: 74 patients (32 M, 42 F; mean age 65 +/-14 years) composed the final study group. Exudative pleural effusion was found in 62 patients; of these 36 were malignant (48.6% of all effusions), 20 parapneumonic (or pleural empyema), and 6 tuberculous. In 12 patients, pleural transudate was diagnosed. The highest diagnostic sensitivity for malignant pleural effusion was found for NSE (94.4% and 80.6% in the pleural fluid and serum, respectively). However, the specificity of NSE measurement was relatively low (36.1% and 47.4% in pleural fluid and serum, respectively). The most specific markers of malignant pleural fluid etiology were pleural fluid CYFRA 21-1 and CEA levels (92.1% and 92.1%, respectively). CA-125 was found to be the most specific serum marker of pleural malignancies (78.9%). The AUC for combined pleural markers was 0.89, combined serum markers 0.82, combined ratio pleural/serum markers 0.88. CONCLUSIONS: There are significant differences between the diagnostic value of various pleural fluid and serum markers. Overall, pleural fluid markers are superior to serum markers in determining the pleural fluid etiology. A combination of two or more tumor markers may help improve their diagnostic accuracy. Pleural fluid and serum measurements of different tumor markers play a limited role in the differentiation between malignant and non-malignant pleural effusions.

Role of bronchoalveolar lavage in the initial diagnosis of smoking-related interstitial lung diseases.

Some of interstitial lung diseases have a potential relation to tobacco smoking and are known as smoking-related interstitial lung diseases (sr-ILD). The aim of this study was to present the typical features in bronchoalveolar lavage fluid (BALF) of patients with sr-ILD with special account to the morphology of alveolar macrophages. We have found typical features of sr-LD in 18 patients with interstitial lung disease. All patients were smokers. Pulmonary function was moderately impaired. Control group consisted of 12 asymptomatic smokers and 18 healthy nonsmokers. The median total cell count in BALF of patients with desquamative interstitial pneumonia was 64.5 x 10(6) and was much higher than in asymptomatic smokers--9.0 x 10(6), and healthy nonsmokers--3.25 x 10(6). A high proportion (mean 90%) and number (55.5 x 10(6)) of macrophages with the predominance of pigmented cells was found. Mean proportion of CD14 positive macrophages was 6%, and of CD54 positive macrophages - 62%. We concluded that features in BALF typical for sr-ILD are uncommon among routinely evaluated specimens, but differ markedly from other forms of ILD.

Premature ventricular complex-induced chronic cough and cough syncope.

The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs). Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow. After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract. Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.

Exercise capacity in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common disease characterized by repetitive partial or complete closure of the upper airway during sleep. Cardiovascular disturbances are the most important complications responsible for increased morbidity and mortality. It is suggested that daytime somnolence, chronic fatigue, and nocturnal hypoxemia may further impair muscle function and decrease exercise fitness. The aim of this study was to evaluate cardiopulmonary response to exercise in OSAS patients. One hundred and eleven middle aged (50.2+/-10 yr), obese (BMI 31.0+/-4.6 kg/m2) patients (109 M, 2F) with severe OSAS (AHI 47.2+/-23.1 h(-1)) were enrolled into the study. OSAS was diagnosed with overnight polysomnography and a symptom-limited cardiopulmonary exercise test was performed on a treadmill using Bruce protocol. The results showed that the most frequent reason for exercise termination were: muscle fatigue and/or dyspnea (66+/-), increase in systolic blood pressure>220 mmHg (20%), ECG abnormalities, and chest pain (6%). Although the mean VO2 peak was within the reference value (29.6+/-6 mlO2/kg/min), in 52 patients (46%) VO2 peak was <84% of predicted. Hypertensive response to exercise was diagnosed in 39 of patients (35%). Patients with severe sleep apnea (AHI40>or=h(-1)) were characterized by higher mean blood pressure at rest, at 25%, 50% of maximal work load, at peak exercise and at post-exercise recovery. Several significant correlations between hemodynamic responses to exercise and sleep apnea severity were also noted. We conclude that exercise tolerance can be limited due to hypertensive response in about 20% of patients. Patients with severe OSAS have exaggerated hemodynamic response to exercise and delayed post-exercise blood pressure recovery. Cardiopulmonary response to exercise seems to be related to sleep apnea severity.

Expression of macrophage surface markers in induced sputum of patients with chronic obstructive pulmonary disease.

The aim of our study was to evaluate cellular content in induced sputum in chronic obstructive pulmonary disease (COPD) in relation to the degree of airway obstruction, macrophage count, and phenotype. We compared the proportion of macrophages and cells expressing the following markers: CD11b, CD14, CD54, and CD71 in induced sputum obtained from patients with mild-to-moderate and severe COPD (n=29)], asymptomatic smokers (n=18), and nonsmokers (n=18). The differential cell count and macrophage phenotypes were examined in induced sputum by immunocytochemistry. We observed a greater proportion of neutrophils and eosinophils and an elevated macrophage count in patients with COPD and in smokers in comparison with nonsmokers. Macrophages in patients with severe airway obstruction were characterized by a significantly elevated expression of CD11b and CD14 markers. There were higher proportions of macrophages with expression of CD11b, CD14, CD54, and CD71 in induced sputum of smokers in comparison with nonsmokers. We concluded that macrophages are the cells involved in the inflammatory process caused by smoking in COPD. The macrophage phenotype with elevated CD11b and CD14 expressions was associated with severe airflow limitation.