Doğanay Alper

Sarcoidosis caused by interferon therapy

Abstract:  Interferon alpha (IFN‐α) is an immunomodulator that is used as an antiviral agent in active chronic viral hepatitis C. IFN therapy can cause an induction or exacerbation of sarcoidosis. Although several reports in the gastroenterology literature have suggested an association between IFN therapy and sarcoidosis, this association has rarely been described elsewhere. A 47‐year‐old woman developed sarcoidosis after cessation of treatment with IFN and ribavirin for chronic hepatitis C. Her sarcoidosis showed liver, pulmonary and skin involvement. She continues to be monitored regularly in the Department of Pulmonary Diseases without steroid therapy. Her sarcoidosis improved spontaneously. We conclude that patients should be monitored for sarcoidosis during and after IFN therapy.

Prognostic significance of blood group antigen expression of tumor tissue in lung cancer patients.

Aims and background Many prognostic factors have been evaluated both for SCLC and NSCLC. The prognostic significance of blood group antigen expression of tumor tissues has been studied particularly in NSCLC, yielding divergent results. The aim of the present study was to investigate the prognostic value of the tumoral expression of blood group antigens ABH in lung cancer. Methods The presence of blood group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 92 patients diagnosed between 1996 and 1997. Monoclonal antibodies were used to detect blood group antigens. Results The median survival was longer in NSCLC patients whose tumors were positive for blood group antigen A (P = 0.009). Since the expression of blood group antigen A in tumor cells was limited to patients with type A or AB blood, survival analysis of these patients showed survival to be longer in non-small cell lung cancer patients with blood group antigen A-positive tumors (P = 0.0019). Conclusions Expression of blood group antigen A in tumor cells is an important, favorable prognostic factor in patients with non-small cell lung cancer, which could be useful to stratify patients with blood group A or AB according to possible outcome, and to guide therapeutic decision-making. The expression of blood group antigens ABH should be evaluated in larger series of lung cancer patients (including small and non-small cell lung cancer) with all blood types.

Exercise capacity in sarcoidosis. Study of 29 patients

BACKGROUND AND OBJECTIVE Sarcoidosis is a systemic granulomatous disease of unknown etiology. Aims of this prospective study are to evaluate degree of impairment in pulmonary function tests (PFT), arterial blood gas analysis (ABG), respiratory muscle strength, exercise capacity and correlation of these parameters with radiological stages; to further evaluate the use of cardiopulmonary exercise testing in assessment of extent of pulmonary disease; and to discuss the pathophysiologic mechanisms of limitation in exercise capacity in patients with sarcoidosis. PATIENTS AND METHOD 29 patients with sarcoidosis were grouped according to their radiological stages (stage I: group 1; stage II, group 2; stage III, group 3). Groups 1, 2 and 3 included 11, 13 and 5 patients, respectively. PFT, cardiopulmonary exercise testing and ABG were performed for each patient. RESULTS Evaluation of all patients showed a significant decrement in exercise capacity. Patients in stage III had decreased diffusing capacity and exercise capacity. There was limitation in exercise capacity in stage I patients who had completely normal spirometry and diffusing capacity. We also found a correlation between radiological stages of the disease and exercise capacity, diffusing capacity and ABG. CONCLUSIONS Exercise capacity is impaired also in early stages of sarcoidosis and it was found to be the earliest impaired physiological parameter in sarcoid patients. Exercise intolerance, having mutifactorial basis, is correlated with radiological stages. Circulatory impairment and impaired heart rate response to exercise have effects on limitation in exercise capacity. Especially in advanced radiological stages of disease, ventilatory and gas exchange impairment also seems to be effective on limiting exercise in patients with sarcoidosis.

Sarcoidosis in Turkey: 1954-2000.

Background Sarcoidosis is a multisystemic disease of unknown etiology. The presentation and frequency of different organ involvement can vary according to race, geographical location and gender. Because of the multiorgan involvement and its mimicking nature, the diagnosis is usually a challenge, even to specialists. Therefore, knowledge of the epidemiologic features of the disease is important. Methods The first case report of sarcoidosis in Turkey was published in 1954. We obtained data from case series by hand searching of journals and congress abstract books on pulmonary medicine between 1954 and 2000. Series of 5 or more cases were included in our compilation of data. Results Data for 1327 patients with the diagnosis of sarcoidosis were obtained from 29 reports. There were nearly twice as many females as males with the disease in these case series. Most of the patients were at stage 1 or 2 at the time of diagnosis. Peripheral lymph node enlargement was reported in 119 patients, skin involvement in 22 and nervous system involvement in 12 patients. Erythema nodosum was reported in 137 patients. Serum angiotensin-converting enzyme was elevated in 52% and the tuberculin skin test was positive in 24% of patients. Organ biopsies seemed to be the preferred diagnostic method in the initial papers while recent papers revealed the value of obtaining a bronchoscope biopsy. Conclusion Despite several limitations of our study, this is the first compilation of 46 years of data on sarcoidosis in Turkey. Further studies on the geographical distribution and incidence and prevalence are needed for our country.

Effects of Losartan on the Renin-Angiotensin-Aldosterone System and Erythrocytosis in Patients with Chronic Obstructive Pulmonary Disease and Systemic Hypertension

AbstractObjective: To evaluate the effects of losartan on blood pressure, erythrocytosis and the renin-angiotensin-aldosterone system (RAS) in patients with erythrocytosis and hypertensive chronic obstructive pulmonary disease (COPD). Design: Prospective, nonrandomised, two-period study. Patients and Participants: 24 patients were recruited, of whom 20 (17 men) completed the trial. The mean age was 55 ± 8 years (range 40 to 65 years). Erythrocytosis was defined as a persistent elevation of the haematocrit to ≥47% in females and ≥50% in males. Patients were ≤65 years of age and hypertensive according to the WHO criteria. Patients who had hepatic and/or renal dysfunction, acute exacerbation of primary disease, were taking systemic corticosteroids, had any other systemic disease, or showed intolerance during the washout period were excluded. Methods: An initial 2-month period on a standard regimen with nasal oxygen (2 L/min, 18 h/day) and bronchodilators (inhaled salbutamol, oral theophylline, inhaled ipratropium bromide) was followed by a second 2-month period during which losartan was administered as an antihypertensive agent in addition to standard therapy. Routine biochemical and haematological monitoring was carried out. Systolic and diastolic blood pressures (SBP and DBP, respectively) were measured. ECG and arterial blood gas analyses were also performed for all patients at the beginning of the study, and all of these clinical and laboratory investigations were performed at 15-day intervals during the study. Plasma renin activity and serum aldosterone and erythropoietin levels were measured both at the beginning and at the end of each 2-month period. Results: No statistically significant changes were found in the measured parameters at the end of the 2-month standard treatment period. Fatigue and dizziness were reported by four of the patients during the first week of losartan treatment. Both SBP and DBP decreased by 10mm Hg with losartan treatment (p = 0.0003 and 0.0002, respectively). Haematocrit decreased from 53 ± 3% to 48 ± 4% (p = 0.0001). The mean arterial blood gas tension of CO2 (pCO2) was 54 ± 11mm Hg and decreased to 48 ± 4mm Hg (p = 0.01). Losartan treatment decreased serum aldosterone to 259 ± 148 ng/dl from a mean baseline value of 156 ± 140 ng/dl (p = 0.03). There were no statistically significant changes in pO2, serum erythropoietin or plasma renin activity. Conclusion: Losartan controls blood pressure and reduces erythrocytosis in patients with hypertensive COPD, and is well tolerated. Although the mechanism of the effect of losartan on erythrocytosis requires further investigation, we propose that the RAS, in particular angiotensin II, has effects on the haemopoietic system and that blocking these effects decreases the haematocrit.