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.

[News in the examination of the ciliary activity in the respiratory tract mucosa]. / Novinky ve vysetování aktivity rasinek sliznice respiracního traktu.

Ciliary activity assessment attracts a great interest and has undergone dynamic progress since the last decades. The ciliary function is typically impaired in primary ciliary dyskinesia (PCD). The cilia are mostly examined in vitro, the sample is taken away from the nasal mucosa. Digital videomicroscopy is accessible for the cilia observation in vitro and represents a gold standard. Manual reading using this method is lengthy in comparison with a photomultiplier. Using the photomultiplier, light captured in an optical fibre is analysed automatically by a computer. With technological progress other methods gain ground such as automatical analysis of variance of grey degrees or photomultiplier connected with a scanning confocal microscope. A medium 199 is mostly used for preservation of the functioning cilia. To retain ciliary beat frequency (CBF) it is necessary to use a heated microscope stage. Average physiological CBF value is 11.5 Hz in adult population and 12.8 Hz in children.

[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.

[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.

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.

[Relation between pulmonary ventilation parameters, exercise tolerance and quality of life in patients with chronic obstructive lung disease]. / Vztah ventilacních plicních parametru, tolerance fyzické záteze a kvality zivota u pacientu s chronickou obstrukcní plicní nemocí.

Patients with chronic obstructive pulmonary disease (COPD) do usually have decreased tolerance of exercise capacity and impaired quality of life. Several studies have shown that exercise capacity is related relatively weakly to lung functions in this group of patients. The aim of the present study was to find parameter which could better reflect or predict maximal exercise capacity. 19 patients with the diagnosis COPD with mean value of forced expiratory volume in one second (FEV1) 46% predicted (range 21-79%) entering pulmonary rehabilitation program were included into the study. Enrolled patients were chosen to cover the whole range of airway obstruction severity. Post-bronchodilator static and dynamic ventilation parameters were used for evaluation and calculation. Quality of live was measured using St. George's respiratory questionnaire (SGRQ), evaluating symptoms, activity and impact of the disease with range from 0 (the best level) to 100 (the worst level). Values of FEV1 (p < 0.001) and ratio of FEV1 to vital capacity (FEV1/VC, p < 0.001) were significantly positively correlated with 6 minute walking distance (6MWD). FEV1/VC were closely related to 6MWD then FEV1. The degree of hyperinflation expressed by residual volume (RV, p < 0.005) and by ratio of residual volume to total lung capacity (RV/TLC, p < 0.001) significantly negatively correlated with 6MWD. Maximal occlusion mouth pressures (PImax, p < 0.05) were positively related to 6MWD. Total score of SGRQ correlated significantly to maximal exercise capacity. Pulmonary function tests and respiratory muscle function have important impact on exercise tolerance in patients with COPD. Tolerance of exercise capacity is significantly reflected by total score of quality of life in this group of patients.

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma]. / Kvalita zivota a tolerance udrzovací lécby u pacientu s mnohocetným myelomem. Ceska myelomova skupina.

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

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.

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.

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.

[Bronchoscopic diagnosis of lung tumours]. / Bronchoskopická diagnostika nádoru plic.

The role of diagnostic bronchoscopy in patients with lung tumours is to evaluate the presence, extent and character of endobronchial tumourous changes. Videobronchoscopes and ultrathin bronchoscopes introduced recently into clinical practice make more accurate evaluation of larger areas of the bronchial tree possible. The clinical impact of methods based on the principle of (auto)fluorescence is searched for. From sites affected with the tumour samples are taken for histological or cytological examination which in addition to evidence of a tumourous etiology specify the type of tumour. An integral part of the examination is staging when the extent of the tumour proper and the regional lymph nodes within the framework of the TNM classification is evaluated optically and by aimed sampling. Examination by endobronchial ultrasound makes it possible to assess more accurately the extent of tumourous affection in the bronchial wall or extrabronchially. The task of the brochologist is also to evaluate the possbility of bronchological intervention (laser, brachytherapy, stent etc.) for palliation of symptoms. Virtual bronchoscopy is the arteficial construction of the image of central airways created from CT scans which makes it possible to visualize sections of the central airways which are not accessible by bronchoscopy. Bronchoscopy is a method of fundamental importance for the diagnosis, therapy and control of complications and palliation of symptoms of lung tumours. This method cannot be replaced at the moment by any other method and its importance is apparent from the fact that the spectrum of bronchoscopic examinations in patients with lung tumours is steadily increasing.

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.

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.