Methotrexate as a single agent for treating pulmonary sarcoidosis: a single centre real-life prospective study.

INTRODUCTION: The first-line therapy in chronic sarcoidosis, according to WASOG/ATS/ERS recommendations, is GCS. This therapy is associated with significant adverse effects and finally does not alter the natural history of the disease. The objective of our study was to evaluate the efficacy and safety of monotherapy with MTX, as an alternative to GCS, in progressive pulmonary sarcoidosis. MATERIAL AND METHODS: An open prospective real-life, single-centre trial was performed on 50 patients with biopsy proven sarcoidosis, 28M and 22F, mean age 45.55 ± 8.9 years. The average duration of disease before MTX therapy was 12.34 ± 20.49 years, GCS therapy in the past was applied in 41 patients. All patients received MTX (10 mg or 15 mg weekly) between 2004 and 2013 because of chronic progressive pulmonary sarcoidosis. Therapy was planned for 24 months. Patients underwent regular clinical evaluation, pulmonary function assessment, exercise ability testing (6MWT), and chest radiography for therapy effectiveness every six months and side effects monitoring every 4-6 weeks. Forty-nine patients were included for statistical analysis of treatment efficacy. They were retrospectively allocated to "MTX responder" group if an improvement of 10% of FEV1, FVC, TLC, or 15% of DLCO from the initial value was documented for at least one parameter or "non-responders" if the patient did not meet the above-mentioned criteria. RESULTS: Duration of treatment ranged from 6 to 24 months, mean time 60.75 ± 34.1 weeks. For the whole cohort significant improvement after MTX therapy was observed for minimal SaO2 (%) (p = 0.043) and for decrease of DSaO2 (%) (p = 0.048) in six-minute walk test. The results were significantly better for patients treated with 15 mg than for those treated with 10 mg weekly and for those who obtained a greater total amount of MTX during therapy. Significant difference of DLCO%pred was observed after six months of MTX therapy between groups treated 15 mg vs 10 mg weekly (73.27 ± 12.7% vs. 63.15 ± 16.4%, p = 0.03). Twenty-five patients (55%) met the criteria of "MTX responders" group. Patients who responded well to treatment had significantly lower TLC and FVC initial values comparing to "MTX non-responders". After treatment the only significant difference in PFT between groups was noted for DLCO%pred. Eleven patients (22%) stopped the treatment due to adverse events of MTX, mild hepatic abnormalities were observed in ten patients (20%), and concomitant infection was found in four patients. There were no patients with a fatal outcome. CONCLUSIONS: MTX as a single agent in the treatment of sarcoidosis has proved to be a safe and effective steroid alternative. Selected patients with chronic pulmonary sarcoidosis experience definite PFT improvements after MTX treatment. There is need to search for predictors of MTX treatment effectiveness.

Impact of mild anaemia on dyspnoea during exertion and exercise tolerance in patients with acute exacerbation of chronic obstructive pulmonary disease.

INTRODUCTION: Dyspnoea and decreased exercise tolerance are symptoms of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Anaemia is a risk factor for reduced functional capacity and dyspnoea in stable COPD. There is limited information about the impact of anaemia on functional capacity and dyspnoea of patients during AECOPD. The aim of this study was to evaluate the impact of decreased blood haemoglobin concentration on the results of six-minute walking test (6MWT) in patients during AECOPD. MATERIAL AND METHODS: A post hoc analysis of data collected from prospective long-term studies on AECOPD. Haemoglobin concentration from the first obtainable hospital measurement were included in the assessment. 6MWT was performed after clinical improvement of the patient. Dyspnoea at baseline and after exercise and oxygen saturation (SpO(2)) during exercise was measured. RESULTS: (presented as means ± SD): 402 patients with exacerbation of COPD (COPD stage 3.5 ± 0.6) were examined. Patients with anaemia (26% of those studied, age 74.5 ± 8.2 years) achieved 258.1 ± 125.1 m during 6MWT, with exertional desaturation of 2.9 ± 2.6%. Patients without anaemia (74% of those studied, age 70.2 ± 8.7 years) achieved 271 ± 136.0 m during 6MWT with exertional desaturation of 3.8 ± 3.7%. The haemoglobin concentration did not correlate with 6MWT, dyspnoea during 6MWT, or exercise oxygenation and blood desaturation during exercise. CONCLUSION: Mildly decreased blood haemoglobin concentration did not influence the results of 6MWT in patients with AECOPD.

[Autoimmunological pulmonary alveolar proteinosis--case report]. / Autoimmunologiczna proteinoza pecherzyków plucnych--opis przypadku.

Autoimmunological pulmonary alveolar proteinosis (APAP) is a rare interstitial lung disease with abnormal surfactant homeostasis. Autoimmunological pulmonary alveolar proteinosis is diagnosed most often in the third or fourth decade of life. Predominant symptoms are dyspnea and cough. In most cases, disease is mild but in more severe cases when dyspnea limits patient physical activity a treatment is required. The most common treatment procedure is a whole-lung lavage. We present a case study of 37 years old woman with the patchy consolidations in the chest radiograph. High resolution computed tomography (HRCT) image suggested hipersensivity pneumonitis. At the beginning due to limited disease symptoms no specific proceedings was implemented. After two year follow-up of non-resolving pulmonary changes the decision about open lung biopsy was made. On the basis of histological examination of samples and presence of anty GM-CSF antibodies the diagnosis of autoimmunological pulmonary alveolar proteinosis was established.

[Six-minute walk test in sarcoidosis patients with cardiac involvement]. / Test 6-minutowego chodu u chorych na sarkoidoze pluc z zajeciem serca.

INTRODUCTION: Cardiac involvement in sarcoidosis is of critical importance, due to the poor prognosis if this organ manifestation is left undiagnosed and untreated. The six-minute walk test (6 MWT) is a useful test to evaluate exercise tolerance of sarcoid patients. We aimed to assess the 6 MWT value in diagnosis, course and treatment monitoring of patients with cardiac sarcoidosis. MATERIAL AND METHODS: 47 patients were included: 22 with pulmonary sarcoidosis and cardiac involvement (13 women, 9 men), 25 with pulmonary sarcoidosis, with no changes in the heart (15 women, 10 men), and 18 healthy volunteers as controls (12 women, 6 men). Out of 22 patients with cardiac involvement 11 were treated for heart sarcoidosis with prednisone (9 pts - initial dose 60 mg daily and 2 pts - 40 mg daily). 11 pts in this group were not treated. In all patients sarcoidosis was confirmed histopatologically. Magnetic resonance imaging was used to diagnose involvement of the heart. In the studied groups we assessed: heart rate (HR), oxygen saturation, and distance in 6 MWT and Borg dyspnea score. RESULTS: Patients with cardiac sarcoidosis desaturated more during exercise (DSaO2max = 3.5 ± 3.2 vs. 0.38 ± 0.69; p = 0.004) and had a lower increase of HR in first minute during the 6 MWT (DHR1 = 21.81 ± 11.72 vs. 50.61 ± 12.35; p = 0.0001) when compared to healthy subjects. Significantly lower increase of HR in first minute of 6 MWT was observed in patients with cardiac sarcoidosis when compared to patients with pulmonary sarcoidosis with no cardiac involvement (DHR1 = 21.81 ± 11.72 vs. 38.8 ± 18.17, p = 0.01). After introduction of treatment in sarcoidosis group, significantly higher (p = 0.02) increase of HR in first minute of 6 MWT as compared to baseline test was observed. CONCLUSIONS: The six-minute walk test is useful in diagnosing cardiac involvement in sarcoidosis. The increase in HR during exercise and decrease degree of desaturation were a good predictors of the response to therapy.

[The impact of comorbidities on the length of hospital treatment in patients with chronic obstructive pulmonary disease]. / Wplyw chorób wspólistniejacych na dlugosc leczenia szpitalnegou chorych z zaostrzeniem przewleklej obturacyjnej choroby pluc.

INTRODUCTION: The aim of this study was to assess relationships of chronic obstructive pulmonary disease (COPD) comorbidities number, with the duration of hospital stay due to acute AE COPD in longitudinal prospective study. MATERIAL AND METHODS: We evaluated the number of re-hospitalizations, length of stay and number of comorbidities in 464 consecutive COPD patients admitted to the tertiary respiratory hospital due to AE COPD enrolled in longitudinal prospective study from 2005 to 2009 year. RESULTS: GOLD II stage COPD patients had 4.1 ± 1.2 comorbidities (p = 0.002), stage III 3.4 ± 1.3 and stage IV had 3.6 ± 1.2 comorbidities. Duration of hospital stay (medians) was longer in more severe patients. Duration of hospitalization correlated with urea level (r = 0.19 p 〈 0.001), pCO(2) (r = 0.193, p = 0.0003), HCO(3) (r = 0.25, p 〈 0.0001), haemoglobin (r = -0.18, p 〈 0.001), and hematocrit (r = -0.13, p = 0.008). The patients with the risk of readmission had more severe GOLD stage and were hypercapnic (pCO(2) = 47.6 mmHg v. 43.9 mmHg in those without hospitalization). CONCLUSIONS: The haemoglobin level, hypercapnia and renal function are predictors of prolonged hospitalization. Patients with more severe airflow limitation and higher pCO(2) have increased risk for readmission to the hospital. More severe disease stage, clinical diagnosis of cor pulmonale or bronchiectasis was related to longer hospital stay.

[Evaluation of motivation to quit smoking in outpatients attending smoking cessation clinic]. / Ocena motywacji do rzucenia palenia u pacjentów poradni antynikotynowej.

INTRODUCTION: The success in smoking cessation depends not only on a method of treatment but also on patient motivation. The aim of this study was to estimate the motivation and the main reason to quit smoking among outpatients attending smoking cessation clinic. MATERIAL AND METHODS: One hundred and eleven patients (50 men and 61 women), mean age 58, filled in a motivation test, nicotine dependence test and a questionnaire of the clinic. RESULTS: The main motivation to quit was for the health reasons (83%). Mean motivation test result was 6.93; mean nicotine addiction evaluated in dependence test was 5.49. Eighty seven percent of patients were ready to quit smoking during one month (36% in 24 hours; 23% in one week; 28% in four weeks). There was no significant difference between men and women. CONCLUSIONS: The main motivation to quit smoking were the health reasons as well among men as women. There was no correlation between the readiness to quit smoking determined as time to quit attempt and the motivation test.

[Simultaneous detection of tumor cells and the positive result of genetic test for Mycobacterium tuberculosis in pleural effusion]. / Jednoczesne wykrycie komórek nowotworowych i materialu genetycznego pratków gruzlicy w plynie oplucnowym.

Pleural effusion is a frequently observed lesion in the course of respiratory diseases such as inflammatory process and cancer metastasis. Its cause may be either tuberculosis (the most common extrapulmonary location is the pleura) and malignant disease of the pleura. Confirmation of tuberculosis is often troublesome. The primary site of cancer may be also difficult to find despite the application of difficult diagnostic methods. Below we present history of 79-year-old female in whom carcinomatous cells and positive result of PCR for Mycobacterium tuberculosis in pleural fluid were discovered simultaneously suggesting the tuberculosis and cancer of unknown primary origin.

[Six-minute walk test in obstructive sleep apnoea]. / Test 6-minutowego chodu u chorych na obturacyjny bezdech senny.

INTRODUCTION: The aim of this study was to assess results of 6MWT in non-selected group of obstructive sleep apnoea (OSA) patients. In healthy adult subjects 6-minute walking distance (6MWD) range from 400 to 700 m. Obesity, the main symptom of OSA, is one of the factors associated with reduction of 6MWD (another common factors: older age, shorter height, female sex, pulmonary, cardiovascular and musculoskeletal diseases). MATERIAL AND METHODS: Subjects completed sleep questionnaire and Epworth sleepiness scale before sleep studies (full polysomnography [PSG] or PolyMesam study [PM]). Consecutive OSA subjects (AHI/RDI >10, Epworth score > 9 points) were evaluated. The 6MWT, chest X-ray, spirometry, arterial blood gases, ECG, blood morphology and biochemistry were performed during trial treatment with autoCPAP. RESULTS: We studied 151 subjects (119 males - 78.8% and 32 females - 21.2%), mean age 53.4 +/- 10.5 years. Subjects were obese - BMI = 35.7 +/- 6.2 kg/m(2) and presented severe OSA - AHI/RDI = 42.4 +/- 23.2. To assess relations between 6MWD and AHI/RDI, BMI, age and concomitant diseases we divided subjects in two groups: 1(st) with 6MWD > or = lower limit of normal (LLN) (123 pts; 81.5%) and 2(nd) with 6MWD < LLN (28 pts; 18.5%). Significant differences between groups were found for BMI, FVC (% of predicted) and Borg dyspnea scale before and after 6MWT. In multiple linear regression analysis we found significant correlation between 6MWD and BMI (beta = 0.41, p < 0.0001) and arterial hypertension (beta = -0.16, p = 0.04). Females had significantly shorter 6MWD than males (401.1 +/- 83.6 m and 451.8 +/- 107 m, respectively; p = 0.01). Difference was significant after adjustment for BMI and age (analysis of covariance) - R = 0.61, R2 = 0.38 (p < 0.0001). CONCLUSIONS: BMI, female sex, arterial hypertension and lower FVC (% of predicted) were related to shorter 6-minute walking distance in OSA patients.

[Xenobiotics influence on estrogen activity]. / Wplyw ksenobiotyków na aktywnosc estrogenów.

Many chemical compounds which imitate estrogens effect are present in the environment. There are natural substances (phytoestrogens), as well as synthetic (xenoestrogens, metaloestrogens) ones. A lot of xenobiotics are inductors or inhibitors of enzymes, also those enzymes which take part in estrogens metabolism. However, little is still known about the influence of xenobiotics on estrogens activity, there can be no question of the importance of the problem. One of them are the diminished effects of endogenous estrogens in women smokers, also weakness or lack of oral hormonal replacement therapy (HRT) effect among women smokers, as well as the influence of estrogens on dioxins toxicity. The issue of estrogen compounds presence in cosmetics deserves special attention. It is essential for us to remember, that estrogens are compounds with high biological activity. Thus, hormonal balance disturbance can have serious health consequences, including tumors. In this research we have attempted to present a review of studies which concern exogenous factors influence on estrogens activity and have summarized current state of knowledge.

[Nocturia in obstructive sleep apnoea (OSA)]. / Nykturia u chorych na obturacyjny bezdech senny (OBS).

INTRODUCTION: Nocturia (two or more urinations per night) is a common symptom in OSA subjects. Higher secretion of atrial natriuretic peptide, increased intra-abdominal pressure, diuretics, diabetes, excessive fluid intake, awakenings are responsible for nocturnal urination. The aim of this study was to evaluate incidence of nocturia in moderate and severe OSA. MATERIAL AND METHODS: We studied 171 consecutive OSA patients (135 males and 36 females) - means: age - 53.6 +/- +/- 10.8 years, AHI/RDI - 43.6 +/- 23.2, BMI - 35.8 +/- 6.3 kg/m(2). RESULTS: To assess relations between nocturia and AHI/RDI, overnight saturation, BMI and daytime sleepiness we divided subjects in two groups: 1(st) - without nocturia - 60 pts; 35.1% (group N-) and 2(nd) - with nocturia - 111 pts; 64.9% (group N+). Group N+ presented with higher AHI/RDI, 48 +/- 22.8 vs. 35.4 +/- 21.7 (p = 0.0006), higher BMI, 36.8 +/- 6.5 vs. 34 +/- 5.5 kg/m(2) (p = 0.004), lower mean overnight SaO(2), 88.6 +/- 5.6 vs. 90.4 +/- 4.3% (p = 0.03) and daytime sleepiness, Epworth score - 14.4 +/- 5.1 vs. 11.3 +/- 5.5 points (p = 0.0002). Multiple linear regression analysis revealed significant correlation between nocturia and Epworth sleepiness score (beta = 0.26, p = 0.0009), coronary artery disease (beta = 0.23, p = 0.004) and AHI/RDI (beta = 0.21, p = 0.04). CONCLUSIONS: Nocturia is frequent in OSA patients (64.9%). Nocturnal urination was related to severity of OSA, excessive daytime sleepiness and coronary artery disease.

The influence of comorbidities on mortality in sarcoidosis: a observational prospective cohort study.

AIM: The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis. MATERIALS AND METHODS: A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality. RESULTS: 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001. CONCLUSION: The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.