Erlotinib in the treatment of advanced squamous cell NSCLC.

Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC). We conducted a large retrospective study based on clinical experience aiming to prove erlotinib's efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity. 1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P<0.001). OS of patients with CR/PR, SD and PD were 13.3, 10.9 and 3.8 months, respectively (P<0.001).The most common adverse effects were rash and diarrhoea. In conclusion ertlotinib is effective and well-tolerated in patients with advanced-stage squamous cell NSCLC.

Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype.

BACKGROUND: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD), whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. METHODOLOGY: An observational study of 98 COPD ex-smokers and subjects from control groups evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern. RESULTS: The NMCCt was decreased in HA compared to those with COPD and decreased in those with COPD compared to those with CF. CBF in COPD was lower compared to HA. The index of ciliary dyskinesia in COPD patients differed from HA. We detected higher NMCCt and lower nasal CBF in patients with chronic bronchitis phenotype (CB) compared to non-CB patients. CONCLUSIONS: We confirmed the presence of impaired nasal MCC in COPD ex-smokers. These impairments were apparent predominantly in the CB phenotype.

Failure of noninvasive prediction of pulmonary hypertension in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Pulmonary hypertension (PH) in patients with advanced idiopathic pulmonary fibrosis (IPF) is a complication connected with unfavorable prognosis. Great efforts have been made in attempting to establish a reliable non-invasive method which would enable detection of this complication. In this context a formula using pulmonary function parameters was published with outstanding results. METHODS: We tested the formula in 27 IPF patients who underwent a lung function examination, cardiac ultrasonography and catheterisation on the same day. RESULTS: Pulmonary hypertension was detected by catheterisation in 17 patients (63%). In our group, contrary to the published data, the aforementioned formula was neither useful for detecting patients with a high probability of PH nor as a means of calculating the mean pulmonary artery pressure in individual patients (p = 0.502 and p = 0.833, respectively). Ultrasound examination reached borderline correlation with the values measured by catheterisation when we compare patients with relevant results (r = 0.531, p = 0.051). However, the examination gave no usable results in 13 patients (48%). CONCLUSION: Our data suggests that no reliable, noninvasive method is currently available for detecting and confirming PH in IPF patients. We did not confirm the usefulness of the published formula. Further carefully organised studies will be necessary to verify or refute it.

[Relationship between quality of life and BODE index of stable ex-smokers with chronic obstructive pulmonary disease]. / Vztah mezi kvalitou zivota a BODE indexem u bývalých kuráku ve stabilní fázi chronické obstrukcní plicní nemoci.

BACKGROUND AND AIM: This study was carried out to assess relationship between quality of life (QoL) and disease severity expressed by multifactorial prognostic index (BODE) in ex-smokers suffering from chronic obstructive pulmonary disease (COPD), minimally 8 weeks free of exacerbation. MATERIALS AND METHODS: The evaluation was performed in 98 randomly recruited COPD patients enrolled into a cross-sectional, observational CILIARY study at the Department of Pneumology, Charles University, Faculty of Medicine in Hradec Králové. In them, quality of life evaluation using the SGRQ questionnaire and the BODE index calculation was performed. We statistically compared interrelationship between BODE and COPD stages, SGRQ and COPD stages and interrelation of BODE and SGRQ. RESULTS: We found significant differences in QoL of COPD patients and QoL in group of healthy volunteers (p <0.001). Lower QoL and higher BODE score were associated with a higher stages of COPD (p < 0.001), with the exception non-significant difference in QoL (SGRQ score) and BODE index between stages I and II. Our study found positive correlation between the all SGRQ scores and multidimensional prognostic BODE index (r = 0.431-0.704). The strongest correlation (r = 0.704) was evident in activity domain of SGRQ. CONCLUSION: Our results proved close correlation ofquality of life (SGRQ) and multidimensional prognostic score (BODE) in stable COPD exsmokers' population. Both these scoring systems are useful tools for the assessment of clinical course and stratification of severity of COPD. However at present both scales are minimally used in the Czech Republic.

[Examination of function and structure of respiratory cilia of adult patients suffering from chronic obstructive pulmonary disease (COPD)--comparison of nasal and bronchial mucosa (pilot of CILIARY STUDY)]. / Porovnání struktury a funkce nazální a bronchiální sliznice u nemocných s CHOPN (pilotní projekt ciliární studie).

INTRODUCTION: Borderline between upper and lower respiratory tract pathology is probably artificial (bronchial asthma). Also inflammation of bronchial mucosa during chronic obstructive pulmonary disease (COPD) is likely combined with inflammatory involvement of nasal mucosa. Ciliary edge of respiratory epithelium is very important part of mucosa layer. AIM: To investigate and compare nasal and bronchial ciliary beat frequency (CBF), degree of nasal and bronchial ciliary dyskinesia, presence of ciliary akinesia and incidence of spinocellular metaplasia in the both mucosa localities among of stable COPD patients (pts). METHOD: Nasal and bronchial mucosa were obtained in the course of bronchoscopy examination of COPD pts in general intravenous anesthesia. Native samples of mucosa tissue were assessed by digital high-speed video microscopy (1,000x magnification). Paired t-test was used to evaluate differences in average frequencies. Significance level was alpha = 0.05. Mode was used to describe "index of dyskinesia", as a measure of association was used K coefficient. MATERIAL: Seventeen COPD pts (6 weeks free of exacerbation) at the age 47-80 (average 64.2 years +/- 9.7) were examined (13 male), average FEV1 61% predic. value (21-81, +/- 15). All patients were active smokers (average 42 pack years +/- 22.8) and all suffered from bronchitic (daily sputum production) phenotype of COPD. RESULTS: We did not find any difference in average ciliary beat frequencies between nose (6.0 Hz +/- 1.3) and bronchus (5.9 +/- 1.3) locality (p = 0.427). We find weak association between nose and bronchus in "ciliary akinesia" (kappa = 0.282) but medium association in "metaplasia" (kappa = 0.485), in index of dyskinesia (kappa = 0.733). CONCLUSION: We did not find in our data any difference in nasal and bronchial ciliary beat frequencies and we found medium association between nasal and bronchial spinocellular metaplasia and index of ciliary dyskinesia. Possible generalization of these results would require further investigation and analysis.

[The role of bronchial artery embolization in the treatment of hemoptysis]. / Postavení embolizace bronchiální tepny v terapii klinicky významné hemoptýzy.

BACKGROUND: Moderate and severe hemoptysis is a potential life-threatening condition which requires immediate medical examination and intervention. AIM: Retrospective evaluation of the effectiveness of bronchial artery embolization in the management of hemoptysis (over 50 ml per 24 hours) in the university hospital (from 1998 to 2005). METHODS: A retrospective case study. Forty seven consecutive patients with hemoptysis over 50 ml per 24 hours were reviewed and data collected from medical documentation (medical history, chest X-ray, bronchoscopy, thorax spiral CT, pulmonary and bronchial angiography). RESULTS: Forty seven patients, 34 men and 13 women aged between 19-87 years, mean age of 57.1 years, were included in this study. All patients had clinically important hemoptysis (more than 50 ml blood in 24 hours), 23 patients 50-200 ml, 14 patients 200-500 ml, 10 patients over 500 ml. Twenty eight patients had reccurent hemoptysis and nineteen patients had the first stage of hemoptysis. Within the study group we recorded the following clinical causes of hemoptysis: 12 COPD with bronchiectasis, 11 pulmonary malignancy, 11 idiopatic hemoptysis, 5 arterioarterial shunts, 3 pneumonia, 2 aspergillomas, 1 posttuberculous scars, 1 pulmonary trauma, 1 pulmonary arteriovenous malformation. All 47 patients underwent angiography. Thirty seven bronchial artery embolizations (BAE) were performed on the side with greater bronchoscopy and CT abnormality. Polyvinyl-alcohol (sponge particles 45-350 pm) or acrylate glue were used as embolizing agents. We did not observe any complication during this procedures (BAE). Immediate success i.e. cessation of hemoptysis was achieved in 36 patients (97%). Follow-up lasted 4-63 months (33 patients). BAE resulted in long-term success i.e. no recurrent hemoptysis for 28 patients (85%). CONCLUSION: Transcatheter bronchial artery embolization is an effective and safe procedure for patients suffering from clinically important hemoptysis. Short-term control of hemoptysis can be achieved in 97% and long-term control in 85% of cases. Bronchial artery embolization is a treatment which can reduce the need for acute thoracic surgery.

Palliative treatment of cancer anorexia with oral suspension of megestrol acetate.

Megestrol acetate (MA) is a progestational agent, currently known as one of the most effective appetite stimulants in patients suffering from cancer anorexia/cachexia syndrome. Oral suspension of this drug may be particularly useful in patients with far advanced disease, where taking larger amount of pills may lead to the decrease of patient compliance. The influence of oral MA suspension on quality of life and nutritional status was evaluated in 22 patients with far advanced cancer suffering from anorexia and more than 5 per cent weight loss, all beyond the scope of anticancer treatment. Most patients had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue scale (VAS) for appetite, anthropometry, maximal handgrip strength and laboratory data were obtained before treatment and then after 2, 4, and 8 weeks of therapy. Despite of a known high mortality in this prognostically unfavorable group of patients (36% within two months in this study), overall quality of life after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite was the most successfully influenced parameter with an improvement in VAS in 95% of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the great majority of patients. Oral suspension of megestrol acetate maybean effective palliative treatment for many patients with far advanced cancer suffering from anorexia/cachexia syndrome.

High dose rate intraluminal brachytherapy in the treatment of malignant airway obstructions.

Endobronchial brachytherapy has been increasingly used in an effort to improve local control and relieve symptoms of malignant airway obstructions. Results of the high dose rate (HDR) intraluminal brachytherapy in 67 patients with inoperable endobronchial tumor treated by combination of teletherapy and brachytherapy with curative (group A ) or palliative (group B) intent, patients with recurrent tumors after previous radiotherapy treated by endobronchial brachytherapy alone (group C), and patients treated by brachytherapy without teletherapy (group D) are presented. Symptomatic improvement was achieved in 66%, 74%, 64% and bronchoscopic response in 70%, 85%, 78% of patients in groups A, B and C, respectively. Median survival was 365, 242 and 884 days from diagnosis and 245, 151 and 153 days from the first brachytherapy application in groups A, B and C, respectively. In group D complete bronchoscopic response was achieved in 3 of 4 patients with early tumor and partial response in 6 of 7 patients with advanced disease. We observed 4 acute and 9 late complications. Brachytherapy is an effective palliative treatment of malignant airway stenosis, but the effect on survival is not apparent.

HDR intraluminal brachytherapy in the treatment of malignant bronchial obstructions.

Symptomatology of malignant intrabronchial obstructions has a serious negative effect on the quality of patients' life. Intrabronchial brachytherapy can play an important role in the palliation of these symptoms. Between December 1996 and September 1998 48 patients suffering from malignant intrabronchial obstructions were treated with intraluminal brachytherapy in the Dept. of Radiation Oncology at the University Maternity Hospital in Brno. Gammamed HDR automatical afterloading equipment was used to treat all patients. The first group (23 patients) was treated with a combination of intraluminal brachytherapy and external radiotherapy. The second group (18 patients who had relapsed after previous external radiotherapy) was given intraluminal radiotherapy only. A third group (7 patients) underwent intraluminal brachytherapy only. In the first group 17 patients (77%) showed symptomatic relief with tumor regression on X-ray in 16 patients and with bronchoscopic regression in 19 patients. Seven patients died before October 1998 having survived 1-6 months after the first brachytherapy application. Sixteen patients are still alive (1-14 months). In the second group, 10 patients (56%) reported significant improvement of symptoms, with endoscopic regression in 12 patients. Twelve patients died before October 1998 surviving 1-6 months after the first brachytherapy session, 6 patients are still alive 1-5 months after the first brachytherapy fraction. In the third group, bronchoscopy confirmed a complete disappearance of intrabronchial lesion in two cases with early intrabronchial tumor. Five patients reported symptomatic improvement with endoscopic regression of the tumor. There was only one complication recorded: bronchospasm in one patient. The short follow up and limited number of patients does not allow comment on the late effects and survival, yet. In conclusion, intraluminal brachytherapy is an effective and safe approach for palliation of malignant bronchial obstructions.

The role of local anaesthetic inhalation during premedication before bronchoscopy.

In a prospective randomized study, the efficacy of local anaesthetic inhalation during premedication before bronchoscopic examination was evaluated. Eighty patients with chronic nonproductive cough were inhaling either nebulized anaesthetics (10 ml of 1% trimecain; 40 patients--group A) or an isotonic chlorine solution (40 patients--group B). This was followed by topical anaesthesia using spray and laryngeal syringe. Comparing the score of cough and episodes of gagging, the inhalation of local anaesthetics appeared to make the procedure slightly more comfortable for some patients. Additional anaesthesia was less frequently needed in group A than in group B (12 vs. 19 patients). However, none of the observed differences reached statistical significance. In conclusion, the inhalation of local anaesthetics at the beginning of premedication before bronchoscopy was not confirmed as a useful method that made the examination more comfortable for patients with chronic non-productive cough, but did produce a moderately beneficial effect in some of them.

Successful bronchoscopic stenting for a 15 mm sized bronchial carcinoid tumour.

A patient with bronchial carcinoid tumour of the right lower lobe is presented. The tumour, although small in extent, and of benign nature, produced complete stenosis of the right lower bronchus, which had to be repaired by inserting an endobronchial stent.

The causes of massive hemoptysis.

In a group of 656 patients examined for hemoptysis of unknown etiology the average amount of expectorated blood in individual diagnostic groups was evaluated and the patients with massive hemoptysis (> 100 ml/24 hrs) were selected. The hemoptysis was evaluated as massive in 53 patients (8%), being most frequent in patients with chronic anatomical changes of lung parenchyma (22/64) and active tuberculosis (4/26). The fact that massive hemoptysis endangers above all patients with bronchiectasis and other anatomical disorders of the lung parenchyma was evident through the comparison of the average maximal amount of expectorated blood, which was significantly higher in this group (78 ml/24 hrs) than in the majority of other diagnoses (total average 22 ml/24 hrs). In conclusion, the risk of sudden massive hemoptysis should be kept in mind in these patients even if only minimal bleeding occurs and energetic cautionary measures should be implemented right from the onset of bloody expectoration.

Commercial polymerase chain reaction test (Amplicor set) in the diagnosis of smear-negative pulmonary tuberculosis from sputum and bronchoalveolar lavage.

The study presents experience with polymerase chain reaction (PCR) in the diagnosis of tuberculosis (TB) and compares the results obtained in sputum and bronchoalveolar lavage fluid (BALF). A total of 1,097 samples from 846 smear-negative patients with suspected TB was examined using PCR and culture during a period of 40 months. TB was the final diagnosis in 160 patients, based on the evidence of mycobacteria in 90 patients and on clinical criteria in the remaining 70. The PCR test had high specificity (98% and 99%, respectively) but poor sensitivity (37% and 34%, respectively) regardless of whether sputum or BALF was examined. Surprisingly, the sensitivity of culture (44% and 35% in sputum and BALF, respectively) was higher than that of PCR in this group. The contribution of BAL to establishing the diagnosis of tuberculosis was rather limited, yet substantial in some patients. The results obtained in this study were compared with the results published in the literature, and it was concluded that further clinical studies are necessary to establish an appropriate role for the polymerase chain reaction in the diagnosis of tuberculosis.

Severe complications following intravesical BCG instillation.

In patients with urinary bladder carcinoma, the intravesical BCG instillation is widely used. We present two cases of severe pulmonary afflictions developed during this treatment. The possible mechanisms of etiology are discussed and the classification of the intravesical BCG treatment side effects is suggested.

Quality of Life Evaluation and Survival Study: a 3-yr prospective multinational study on patients with chronic respiratory failure.

Therapy of patients with chronic respiratory failure is mainly directed at minimizing symptoms in order to improve, or at least to prevent a deterioration of, patients' well-being. Under such circumstances, the perceived effect of therapies on patients' well-being and daily life represents the most important subjective outcome of treatment. Therefore, there is a need to provide a global estimate of health in patients on long term oxygen therapy or overnight home mechanical ventilation. The Maugeri Foundation Respiratory Failure Questionnaire (MRF28) is the first health status ("quality of life") questionnaire specifically developed for use in CRF and its items were selected to be applicable to patients with both obstructive and restrictive diseases. The Quality of Life Evaluation and Survival Study (QuESS) is a multinational study with the aim of re-evaluating the natural history of chronic respiratory failure in about 300 patients. To the authors knowledge, the Quality of Life Evaluation and Survival Study is the first study to evaluate the natural history of chronic respiratory failure in such a large number of subjects and with a complete set of data. In fact, both pathophysiologic and health status assessments will be made. Moreover, by collecting data on mortality, disease exacerbations and hospitalization, it will also be possible to verify the predictive ability of health status versus pathophysiology in terms of mortality and healthcare utilization.

[Why evaluate the quality of life in patients with bronchial obstruction?]. / Proc hodnotit kvalitu zivota nemocných s bronchiální obstrukcí?

Quality of life, more precisely health related quality of life, is gaining basic importance in evaluating of patient's health status and results of medical interventions. On the example of patients with bronchial obstruction is demonstrated that quality of life evaluation, although not usually used in clinical practice yet, is in significant correlation with some of usual clinical measures; moreover, it brings otherwise inaccessible information about patient's subjective assessment of his disease and his health situation.

[New and old definitions and COPD terminology]. / Nové a staré definice a názvosloví u CHOPN.

Terminology of the disease currently known as chronic obstructive pulmonary disease has gone through a long and non-uniform development. Various definitions have been gradually developed and chronic bronchitis was separated from pulmonary emphysema. Various umbrella names have been suggested to unite this group of diseases. At present a classification based on World strategy for diagnosing, treatment and prevention of the chronic obstructive pulmonary disease from 2000 which has been published in our country too is used.