Tuberculosis treatment outcome in Thessaloniki, Greece - a single center study.

BACKGROUND: Greece is one of the few countries in the European Union/European Economic Area, which do not report tuberculosis (TB) treatment outcome. This study aimed to assess treatment outcomes and identify possible intervening factors in patients with TB in Thessaloniki, Greece, over the period 2012-2017. METHODS: All patients diagnosed with TB -excluding rifampicin-resistant/multidrug-resistant (RR/MDR)-TB- during 2015-2017 were included in the study. Data on demographic characteristics, localization, diagnostic methods, resistance, and treatment outcome were recorded and compared to the period 2012-2014. RESULTS: During the period 2015-2017, 82 patients (48 men) with a mean age of 53.8 ± 15.6 years were diagnosed with TB. No significant differences in demographics, microbiological, or treatment characteristics were detected between the two three-year periods, except for the percentage of immunocompromised patients, which was higher during 2015-2017 (15.9 % vs 5.6 %, p =0.029). In the total number of patients, two factors were significantly different between patients with a positive and negative outcome. The percentage of favorable outcome was higher for patients with extrapulmonary compared to pulmonary TB (90.9 % vs 70.5 %, p =0.044). Furthermore, the percentage of immunocompetent patients with a positive outcome was significantly higher in the second treatment period compared to the first (treatment success rate 66.7 % in 2012-2014 vs 84.1 % in 2015-2017, p =0.014). This difference was attributed to the presence of a social nurse who joined the center in 2015. CONCLUSIONS: TB treatment success rate in Greece is below the World Health Organization standards. Interventions such as appropriate multidisciplinary staffing of TB centers may prove valuable in improving TB care in Greece. HIPPOKRATIA 2019, 23(4): 154-159.

Exhaled nitric oxide as screening tool in subjects with suspected asthma without reversibility.

BACKGROUND: As fractional exhaled nitric oxide (FeNO) has been evaluated only in certain settings for asthma diagnosis, we investigated whether FeNO values could predict positive methacholine challenge testing (expressed as PD20) in subjects with suspected asthma but without spirometric reversibility. METHODS: Subjects with asthma-like symptoms and negative bronchodilation test were initially evaluated to undergo FeNO measurement and methacholine bronchial challenge. Diagnostic performance of FeNO to predict PD20 to methacholine <800 µg was examined by constructing receiver-operating characteristic curves. RESULTS: A total of 112 subjects met the inclusion criteria. In all subjects, FeNO >32 ppb was associated with a sensitivity of 0.47 and a specificity of 0.85 for the identification of the PD20 <800 µg (AUC = 0.691, 95% CI = 0.6-0.775, p = 0.00002). In smokers, FeNO >11 ppb was associated with a sensitivity of 0.85 and a specificity of 0.5 for the identification of PD20 <800 µg (AUC = 0.625, 95% CI = 0.45-0.772, p = 0.18), while in atopics a FeNO level >26 ppb was associated with a sensitivity of 0.55 and a specificity of 0.85 (AUC = 0.677, 95% CI = 0.53-0.8, p = 0.02). CONCLUSIONS: In subjects with symptoms compatible with asthma but without spirometric reversibility, specific cutoff levels for FeNO levels significantly predict the positive methacholine challenge, with significant confounding factors being atopy and current smoking.

Management of malignant pleural effusion by suicide gene therapy in advanced stage lung cancer: a case series and literature review.

Gene therapy can be defined as the transfer of genetic material into a cell for therapeutic purposes. Cytosine deaminase (CD) transferred into tumor cells by an adenoviral vector (Ad.CD), can convert the antifungal drug fluorocytosine (5-FC) to the antimetabolite 5-fluorouracil (5-FU), which kills not only the transfected tumor cells but also their neighbors by the so-called 'bystander effect'. After testing a protocol for Ad.CD transfer and lung tumor burden control in a Lewis mouse model, we used this technique in the management of lung cancer patients with malignant pleural effusion (MPE): two cases are presented investigating the possible enhancement of anticancer effect in both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) by local activation of the pro-drug 5-FC. Results were discussed in parallel to a literature review on the topic. 5-FC and Ad.CD were administered intratumorally to Lewis mouse lung carcinoma and the effect was monitored by tumor size and electromicroscopy. Two patients with advanced stage lung cancer (1SCLC, 1NSCLC), which developed MPE during first-line treatment were administered 10(12) plaque-forming unit (pfu) Ad.CD by intrapleural instillation, in two doses (day 1 and day 7). Instillation was performed when the pleural fluid was ≤200 ml. In addition, they received 5-FC 500 mg four times daily for 14 days. Lung tumor regression and successful transfer of adenoviral particles were observed in treated animals. Patients presented complete regression of pleural effusion as monitored by computerized tomography scan. Neutrapenia and anemia were the most severe adverse effect presented (grade III/grade IV 100%). The increased toxicity followed by the intrapleural gene therapy indicates the augmentation of anticancer effect of transformed pro-drug 5-FC to active 5-FU. The obtained data indicate that intrapleural gene therapy may be a useful tool, adjunct to chemotherapy, in the management of MPE related to lung cancer.

Levels of inflammatory mediators in chronic obstructive pulmonary disease patients with anemia of chronic disease: a case-control study.

BACKGROUND: Although a subset of patients with chronic obstructive pulmonary disease (COPD) display anemia, the role of elevated pro-inflammatory cytokines in COPD-related anemia of chronic disease (ACD) has not been fully investigated. AIM: To examine the levels of interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), C-reactive protein (CRP) and erythropoietin in stable COPD outpatients with and without ACD. DESIGN: A case-control design was followed. METHODS: Fifty-four patients with stable COPD were studied. Among them, 27 had ACD according to strict clinical and laboratory criteria (group of cases), while another 27 nonanemic COPD patients, carefully matched to cases for age, gender, height, lung function and smoking status represented the controls. Serum levels of IL-1ß, IL-6, IL-10, TNFα, IFNγ, CRP and erythropoietin were measured in both groups. RESULTS: Patients with ACD had significantly higher levels of IL-10 [25.6 (1.9-95.2) vs. 4.1 (1.9-31.9) pg/ml, P = 0.049] and IFNγ [15.2 (2.2-106.9) vs. 2 (1.2-18.3) pg/ml, P = 0.026] and had more frequently elevated CRP than controls. Levels of IL-1ß [26.2 (9.8-96.4) vs. 7.9 (2.1-28.4) pg/ml, P = 0.073], IL-6 [20.3 (2.1-125.4) vs. 6.2 (1.2-33.8) pg/ml, P = 0.688] and TNFα [30.1 (3.2-107.5) vs. 10.1 (3.2-50.4) pg/ml, P = 0.131] were also higher in cases, but the differences did not reach statistical significance. Patients with ACD also displayed significantly higher erythropoietin levels than controls [(21.9 (8.4-101.7) vs. 9.7 (6.3-21.7) mIU/ml, P = 0.010], indicating erythropoietin resistance. CONCLUSION: This study shows that in stable COPD outpatients with strictly defined ACD, levels of inflammatory mediators and erythropoietin are elevated compared to nonanemic controls.

Bronchoalveolar lavage fluid alteration in antioxidant and inflammatory status in lung cancer patients.

BACKGROUND: Increased oxidative and inflammatory markers have been reported in lung cancer patients, but relatively few studies have investigated the presence of antioxidants both in the local lung environment and in the systemic circulation. Furthermore, it is hypothesized that the immune system activation in vivo is regulated by the redox environment. OBJECTIVES: To investigate local and systemically circulating antioxidant and inflammatory mediators in lung cancer patients and potential correlations between them. METHODS: Forty two male patients (mean age 65±8years) with primary lung cancer were studied. Sixteen age and smoking history matched male subjects without any evidence of malignancy served as controls. Total antioxidant status (TAS) and glutathione (GSH), as well as interleukin-1a (IL-1a), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in bronchoalveolar lavage fluid (BALF) and serum samples. RESULTS: A statistically significant increase of TAS and GSH in BALF was observed in lung cancer patients compared to healthy subjects (0.27±0.24 vs. 0.12±0.02mmol/L, p=0.02 and 7.56±4.29 vs. 4.62±2.23µmol/L, p=0.01 respectively). Statistically significant correlations in cancer patients were observed in BALF between TAS and a. IL-1α (r=0.87, p<0.001), b. IL-6 (r=0.52, p=0.001) and c. TNF-α (r=0.67, p<0.001). CONCLUSIONS: Alteration in antioxidant and inflammatory mediator status was found in lung cancer patients both in serum and in BALF compared to healthy subjects matched for smoking history. Moreover, a positive correlation was observed between antioxidants and pro-inflammatory cytokines, but only locally and not systematically.

A 26-year-old male with mesothelioma due to asbestos exposure.

Mesothelioma is a malignancy with poor prognosis, with an average 5-year survival rate being less than 9%. This type of cancer is almost exclusively caused by exposure to asbestos. A long exposure can cause mesothelioma and so can short ones, as each exposure is cumulative. We report a case of a 26-year-old male who was exposed to asbestos during his primary school years from the age of 6 to 12. Although the tumor mainly affects older men who in their youth were occupationally exposed to asbestos, malignant mesothelioma can also occur in young adults. A medical history was carefully taken and asbestos exposure was immediately mentioned by the patient. We conducted biopsy on the right supraclavicular lymph node. The patient was not a candidate for surgery, and chemotherapy treatment was initiated. While patient's chemotherapy is still ongoing, no other similar cases of students or teachers have been traced up to date from his school. The school building was demolished in January 2009.

Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters.

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Exophthalmos as a first manifestation of small cell lung cancer: a long-term follow-up.

Small cell lung cancer is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic therapy, until now treatments have failed to control or cure this disease in most patients. Orbital metastases are a rare manifestation of systemic malignancies. Breast and lung cancers represent more than two thirds of the primary cancer sites. Metastases to the eye and orbit develop in approximately 0.7-12% of patients with lung cancer. Here, we report a rare case of exophthalmos as the first manifestation of a metastatic carcinoma due to small cell lung cancer, and a 6-months follow-up with complete exophthalmic response to chemotherapy.

Alterations of erythrocyte superoxide dismutase activity in patients suffering from asthma attacks.

BACKGROUND: Oxidant-antioxidant imbalance may play an important role in the development and progression of bronchial asthma. However, the role of blood antioxidants especially in asthma exacerbation has not been fully discussed. OBJECTIVE: This study examines a part of the intracellular antioxidant defense mechanism in asthmatic patients admitted to hospital due to severe exacerbation of their disease. METHODS: Peripheral blood Erythrocyte Superoxide Dismutase (SOD) activity was measured in 38 patients (33 men - 5 women, with a mean age of 56 +/- 2.8 yrs), using a colorimetric method. On the days of admission and discharge the Forced Expiratory Volume in 1 second (FEV1) and the Partial arterial Oxygen pressure (PaO2) were recorded and correlated with SOD activity at the same time. RESULTS: A statistically significant decrease of SOD activity was observed on the day of admission compared to SOD activity on the day of discharge (43.64 +/- 31.78 vs. 96.16 +/- 54.05 units/ml, p < 0.001), suggesting the presence of oxidative stress during an asthma attack. A statistically significant correlation was observed between FEV1 on admission and SOD activity at the same time (r = 0.57, p < 0.001). Furthermore, SOD activity on admission was correlated with PaO2 on discharge (r = 0.55, p < 0.001), as well as SOD on discharge with PaO2 on discharge (r = 0.53, p = 0.001). CONCLUSIONS: Decreased systemic erythrocyte SOD activity was observed during asthma attacks. This activity was correlated with severity criteria such as FEV1 and PaO2. Therefore, it seems that measurement of SOD activity could be a useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in the future needs further clarification.

Bronchoalveolar lavage fluid eosinophils are correlated to natural killer cells in eosinophilic pneumonias.

BACKGROUND: Eosinophilic lung diseases comprise a group of heterogeneous pulmonary disorders linked by increased eosinophils in bronchoalveolar lavage fluid (BALF). There is supporting evidence that natural killer (NK) cells participate in the regulation of eosinophilic inflammation. OBJECTIVE: Our aim was to investigate the relationship between eosinophils and NK cells in BALF in patients with different interstitial lung diseases (ILDs) focusing on eosinophilic pneumonias. METHODS: Of 114 patients who presented with increased BALF eosinophils (>5%), 74 patients were classified into the following groups: 27 had eosinophilic pneumonia (EP), 17 had idiopathic pulmonary fibrosis (IPF), 16 had hypersensitivity pneumonitis (HSP) and 14 had cryptogenic organizing pneumonia (COP/BOOP). Total BALF cells, cell density and cell differential counts were assessed and lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3-CD16/56+ (NK) and CD3+CD16/56+ (NKT) were determined by flow cytometry. RESULTS: Significant differences were observed in the percentages of lymphocytes (p < 0.001) and CD3+CD16/56+ cells (p = 0.023) among patient groups. In patients with EP, the percentage of eosinophils correlated positively with the number of CD3-CD16/56+ cells (r = 0.522, p = 0.005), the percentage of CD3-CD16/56+ cells (r = 0.690, p < 0.001), and the absolute count of CD3+CD16/56+ absolute cells (r = 0.609, p = 0.001). However, in patients with IPF, HSP or COP/BOOP, no correlation between the percentage of eosinophils and CD3-CD16/56+ or CD3+CD16/56+ cells was observed. CONCLUSIONS: Eosinophil inflammation seems to develop through a different pathway in EP compared to other ILDs.

Epidemiologic trends in lung cancer over two decades in Northern Greece: an analysis of bronchoscopic data.

BACKGROUND AND AIM: The relative frequency of histological subtypes of lung cancer in Europe has changed dramatically during the 20th century. The aim of this study was to explore the changing epidemiology of lung cancer in Northern Greece over the last two decades. METHODS: From the extensive database of the Bronchoscopy Unit of the G. Papanicolaou General Hospital, Thessaloniki, Greece, we identified all patients with a histologic and/or cytologic report positive for lung cancer over two consecutive decades. RESULTS: Between 1/1/1986 and 31/12/2005 we identified 9981 patients with specimens positive for lung cancer. A significant increase in mean patient age was observed during the second decade (64.8 +/- 9.4 vs. 62.1 +/- 8.9, p=0.001). Men developed lung cancer ten times more often than women. The predominant histological type was squamous cell cancer in males (4203 cases, 45.7%) and adenocarcinoma (418 cases, 52.6%) in females. The number of lung cancer cases was significantly higher during the second decade compared to the first decade (5766 cases [57.8%] vs. 4215 cases [42.2%], respectively, p<0.001). There was a significant decrease in the percentage of squamous cell carcinoma in males in the second decade (2317 cases [44.1%] vs. 1886 cases [48.0%], p<0.001), and an increase in adenocarcinoma (1021 cases [19.4%] vs. 609 [11.6%], p<0.001). In females, the relative incidence of adenocarcinoma was decreased and that of squamous cell carcinoma was increased, but not significantly. There was no obvious change in the incidence of small cell lung cancer. Neoplastic lesions were most often located in the upper lobes. CONCLUSION: The number of lung cancer cases has increased in the last decade. Squamous lung cancer appears to be decreasing in men and increasing in women. Adenocarcinoma appears to be increasing in men and decreasing in women. There appears to be no change in small cell lung cancer. During the second decade there has been a significant decrease in the male: female ratio.

Left ventricular diastolic dysfunction in idiopathic pulmonary fibrosis: a tissue Doppler echocardiographic [corrected] study.

It was hypothesised that, apart from right ventricular (RV) dysfunction, patients with idiopathic pulmonary fibrosis (IPF) also exhibit left ventricular (LV) impairment, which may affect disease progression and prognosis. The aim of the present study was to evaluate LV performance in a cohort of IPF patients using conventional and tissue Doppler ECG. IPF patients exhibiting mild-to-moderate pulmonary arterial hypertension (mean age 65+/-9 yrs; n = 22) and healthy individuals (mean age 61+/-6 yrs; n = 22) were studied. Conventional and tissue Doppler ECG were used for the evaluation of RV and LV systolic and diastolic function. In addition to the expected impairment in RV function, all patients showed a characteristic reversal of LV diastolic filling to late diastole compared with controls (early diastolic peak filling velocity (E)/late diastolic peak filling velocity 0.7+/-0.2 versus 1.5+/-0.1, respectively). Patients with IPF also exhibited lower peak myocardial velocities in early diastole (E(m); 5.7+/-1.1 versus 10.3+/-1.6 cm x s(-1), respectively), higher in late diastole (A(m); 8.9+/-1.3 versus 5.5+/-0.8 cm x s(-1), respectively), lower E(m)/A(m) ratio (0.6+/-0.1 versus 1.9+/-0.5, respectively) and higher E/E(m) ratio (10.8+/-3 versus 6+/-0.6, respectively), all indicative of LV diastolic dysfunction. Moreover, LV propagation velocity was significantly lower in IPF patients (46+/-13 versus 83+/-21 cm x s(-1), respectively). Physicians should be aware that patients with idiopathic pulmonary fibrosis exhibit early impairment of left ventricular diastolic function.

Expiratory flow limitation in patients with pleural effusion.

BACKGROUND: Expiratory flow limitation (EFL) is one of the main mechanisms contributing to dyspnea in patients with chronic obstructive pulmonary disease but has not been explored in patients with pleural effusion. OBJECTIVES: It was the aim of this study to determine whether patients with pleural effusion exhibit EFL and to investigate the effect of therapeutic thoracentesis on EFL. PATIENTS AND METHODS: The study was performed on 21 patients with pleural effusion who were subjected to thoracentesis and measurement of pleural pressure (PP). Spirometry and estimation of flow limitation by the negative expiratory pressure technique were performed before and after thoracentesis. RESULTS: Statistically significant differences were observed in all spirometric parameters. No correlation between the increase in lung volumes and flows and any of the aspirated fluid parameters was observed. Before thoracentesis, 14 out of 21 patients were flow limited, compared with 7 patients after thoracentesis (chi(2) = 6.151, p = 0.013). Mean values of flow limitation before and after thoracentesis differed significantly. The decrease in flow limitation did not correlate with the increase in the spirometric parameters, the aspirated fluid volume or PP decrease. CONCLUSIONS: In the majority of patients with pleural effusion, flow limitation improves after thoracentesis. Flow limitation may be a contributing factor to the sensation of dyspnea in these patients.

Total antioxidant status and severity of community-acquired pneumonia: are they correlated?

BACKGROUND: Oxidant/antioxidant imbalance has been reported in various respiratory diseases including pneumonia. However, the role of blood antioxidants has not been fully discussed. OBJECTIVES: The aim of this exploratory study was to assess serum total antioxidant status (TAS) in patients with community-acquired pneumonia (CAP) and the probable correlation with the severity of the disease. METHODS: Thirty patients (22 men, 8 women; mean age of 48 +/- 21 years) and 10 healthy nonsmokers (mean age 44 +/- 16 years) were studied. Clinical, laboratory and radiological findings were recorded on the day of admission and on the 7th day. A severity score was calculated using the Fine scale. Serum TAS was measured at the same time points using a colorimetric method. RESULTS: On admission, TAS (TAS1) was significantly lower than on the 7th day (TAS2) (0.84 +/- 0.13 mmo/l vs. 1.00 +/- 0.17 mmo/l; p = 0.0001) and compared with the healthy subjects (0.84 +/- 0.13 vs. 1.19 +/- 0.09 mmol/l; p < 0.001). TAS change (TAS2 - TAS1) was statistically significantly more marked in smokers (0.17 vs. 0.28, p = 0.001), in patients with factors predisposing to CAP (0.12 vs. 0.37; p = 0.000) and in patients with gram-negative pneumonia (0.16 vs. 0.35; p = 0.000). On the other hand, change in TAS was statistically significantly less marked in patients with lobar pneumonia (0.27 vs. 0.17; p = 0.001). Additionally, TAS change was positively correlated to white blood count on admission (r = 0.39; p = 0.029). CONCLUSIONS: It is concluded that serum TAS is decreased in patients with CAP, suggesting the presence of oxidative stress, and that change in TAS seems to be influenced by disease severity. TAS measurement may be useful in estimating the severity of CAP and is a probable indication for the administration of antioxidants in the management of the disease.

Serum total antioxidant status in severe exacerbation of asthma: correlation with the severity of the disease.

Oxidative processes, mediated by oxygen free radicals are recognized to contribute significantly to the inflammatory pathology of bronchial asthma. An imbalance between oxidants and antioxidants has also been proposed in this disease. This study examines the serum total antioxidant status (TAS) in asthmatic patients with severe exacerbation of their disease and the probable correlation with clinical or laboratory findings. The TAS was measured in 20 patients (10 men and 10 women, with a mean age of 41.95 +/- 20.75 years), using a colorimetric method. On the days of admission and discharge, the forced expiratory volume in 1 sec (FEV1), the partial arterial oxygen pressure (PaO2), and severity criteria were recorded and correlated with TAS at the same time. The TAS was also measured in 10 healthy subjects (8 men and 2 women, mean age of 39 +/- 9 years). A statistically significant decrease of TAS was observed on admission day compared to that on discharge day (0.98 +/- 0.08 vs. 1.12 +/- 0.17 mmol/L, p < 0.001, respectively, paired t-test) suggesting the presence of oxidative stress during an asthma attack. The TAS on admission was also statistically significantly decreased compared to that of normal subjects (0.98 +/- 0.08 vs. 1.19 +/- 0.09 mmo/L, p < 0.001, respectively, paired t-test). A statistically significant correlation was observed between FEV1 change and TAS change, from admission to discharge day (r = 0.58, p = 0.007, Pearson correlation). Finally, a statistically significant correlation was found between FEV1 change and TAS on discharge day (r = 0.65, p = 0.002). Decreased TAS was found during an asthma attack, probably as a consequence of increased oxidative stress. The TAS change was correlated with severity criteria, such as FEV1. Therefore, it seems that measurement of TAS could be a simple and useful tool in the evaluation of an asthma attack. The supplementary administration of antioxidants in future needs further clarification.

A Phase II study of docetaxel and carboplatin in the treatment of non-small cell lung cancer.

We investigated the efficacy of docetaxel (D) in combination with carboplatin (C) in the treatment of non-small cell lung cancer (NSCLC) patients. Since 1996, 123 with inoperable NSCLC were enrolled in the study; 120 (108 males, 12 females; mean age 58.0+/-8.3 years) were evaluated. Of those, 46 patients had squamous carcinoma, 44 adenocarcinoma, 11 large cell carcinoma and 19 undifferentiated tumours. Eligibility criteria included, documented inoperable NSCLC, WHO performance status (PS) 0-1, age up to 70 years, and normal renal and hepatic function. A total of 622 cycles of chemotherapy (CHT) (median 7 (95% CI 6.2-7.47), courses per patient) were administered. Each cycle consisted of 100 mg/m(2) of docetaxel in a 2-h infusion with C at a dose of area under the curve (AUC) of 6 on day 1. This regimen was repeated every 28 days up to eight cycles. Of the patients, five (4%) achieved complete response, 49 (40%) partial response, 47 (39%) had stable disease and 19 (15%) had progressive disease. The median survival was 12 months for all patients, 12 for the four patients with stage IIb disease, 18 for the patients with stage IIIa disease, 20 for the 29 patients with stage IIIb disease, and 11 for the 65 stage IV patients. The median time to progression was 8 months (90 patients). Toxicity was, grade 3/4 neutropenia, 18 patients (15%); grade 3/4 anaemia, 6 patients (5%); and tolerable peripheral neuropathy, 16 patients (13.3%). Responders received radiotherapy (total dose, 50 Gy in 4 weeks) between the 6th and 8th cycle. Among responders with initial stage IIIb disease, 7 (5%) underwent surgical resection. Patients with early progression of the disease received the same dose of radiotherapy between 2nd and 3rd cycle. The study is ongoing, and six patients (5%) are still alive (after 3 years). Preliminary results indicate that the D/C combination is very active in the treatment of NSCLC with tolerable toxicity. It appears that this drug combination is also good as neoadjuvant therapy in inoperable NSCLC patients.

Hering-Breuer reflex in normal adults and in patients with chronic obstructive pulmonary disease and interstitial fibrosis.

BACKGROUND: It has been suggested that the Hering-Breuer reflex (HBR) is unimportant in adults during normal tidal breathing and that it is elicited only if tidal volume is increased above a certain critical threshold. OBJECTIVE: The aim of this study was (1) to study the occurrence of the HBR in adults with normal pulmonary function and (2) to examine if changes in lung mechanics have any effect on the HBR. METHODS: We examined 11 adults with normal pulmonary function, 8 patients with chronic destructive pulmonary disease (COPD) and 3 with interstitial fibrosis (IF). All subjects were lightly sedated with fentanyl, intubated and ventilated with a Servo-900 ventilator. Inspiratory and expiratory flow (and after integration, volume) and mouth pressure were recorded from the endotracheal tube with a pneumotachograph and a pressure transducer. Pressure support ventilation was applied in all patients and functional residual capacity (FRC) was measured with the N(2) washout method. Mean (Te(mean)) and maximal expiratory time (Te(max)) were determined for each individual for 20 breaths. Following several breaths to establish a stable baseline the airway was occluded at end inspiration by a shutter. A positive HBR was interpreted as longer Te(occ) than Te(max) (Te(occ)/Te(max), %). Occlusion was maintained until negative airway pressure occurred and the occlusion time (Te(occ)) was measured. We attempted occlusions after the addition of 5 cm H2O positive end-expiratory pressure (PEEP) and subsequently with 10, 15 and 20 cm H(2)O PEEP. Te(occ) was measured of progressively larger lung volumes. To examine the HBR sensitivity in the three groups, we plotted the lung volumes of occlusion against the corresponding Te(occ)/Te(max). RESULTS: The ratio Te(occ)/Te(max) increased from 167.5 +/- 82.5 at normal FRC to 474 +/- 200.2 s (PEEP(20)). On the contrary, in patients with COPD, Te(occ)/Te(max) increased from 125.2 +/- 34 to 193.7 +/- 74.2 (p < 0.05). CONCLUSIONS: The HBR was positive in all subjects. COPD patients were found to be less sensitive to volume changes when compared with normal controls and with IF patients.