Fusun Oner Eyuboglu

The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement

Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-&ggr; based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.

Risk Assessment of Tuberculosis in Immunocompromised Patients. A TBNET Study

RATIONALE In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Clinical, radiologic, and functional evaluation of 304 patients with bronchiectasis

BACKGROUND: Bronchiectasis continues to be one of the major causes of morbidity and mortality in developing countries, with a probably underestimated higher prevalence than in developed countries. OBJECTIVE: To assess the clinical profile of adult patients with bronchiectasis. METHODS: We retrospectively reviewed the clinical, radiologic, and physiologic findings of 304 patients with bronchiectasis confirmed by high-resolution computed tomography. RESULTS: Mean age of participants (45.7% males, 54.3% females) was 56 ± 25 years and 65.8% of them were lifetime non-smokers. Most common identified causes of bronchiectasis were childhood disease (22.7%), tuberculosis (15.5%), and pneumonia (11.5%). The predominant symptoms were productive cough (83.6%), dyspnea (72%), and hemoptysis (21.1%). The most common findings on chest examination were crackles (71.1%) and rhonchi (28.3%). Types of bronchiectasis were cylindrical in 47%, varicose in 9.9%, cystic in 45.1%, and multiple types in 24.3%. Involvement was multilobar in 75.3% and bilateral in 62.5%. Of 274 patients, 20.8% displayed normal pulmonary function test results, whereas 47.4%, 8% and 23.7% showed obstructive, restrictive, and mixed pattern, respectively. Patients with cystic disease had a higher frequency of hemoptysis (42%) and a greater degree of functional impairment, compared to other types. CONCLUSION: In patients with bronchiectasis from southern Turkey, generally presenting with recurrent productive cough, hemoptysis, dyspnea, and persistent bibasilar rales, the etiology remains mainly idiopathic. Post-infectious bronchial destruction is one of the major identified underlying pathological processes. The clinical picture and the deterioration of the pulmonary function test might be more severe in patients with cystic type bronchiectasis.

Genetic Mutations in Turkish Population With Pulmonary Embolism and Deep Venous Thrombosis

Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients (P = .04) with allele frequency of 6.3% (P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients (P = .001) with allele frequency of 6.9% (P = .003). MTHFR 677TT genotype was significantly higher in patients (P = .009) with allele frequency of 23.8% (P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies (P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.

Pulmonary Function in Uremic Patients on Long‐term Hemodialysis

Twenty patients with end‐stage renal failure who were on maintenance hemodialysis (HD) underwent pulmonary function testing (PFT) before and shortly after an HD session. On pre‐HD PFT, the mean values of all parameters except residual volume (RV) were in the normal range. Mean RV was high (152.9%), and mean diffusing capacity of the lung for carbon monoxide (DLCO) was high‐normal (110.4%). The pre‐HD static inspiratory (PImax) and expiratory pressures (PEmax) were much lower than normal (67.4% and 36.3%, respectively). After the HD session, repeat PFT revealed a small increase in expiratory flow rates, and a significant drop in PImax. There was a strong correlation between PImax and PEmax (r = 0.567, p < 0.01) at the pre‐ and post‐HD stages, indicating that common mechanism(s) are responsible for impairment of both inspiratory and expiratory muscle strength. The well‐preserved DLCO was thought to be due to the use of biocompatible dialyzer membranes. Chronic vascular congestion might be the other explanation of high DLCO.

The Prevalence and the Impact of Portopulmonary Hypertension on Postoperative Course in Patients Undergoing Liver Transplantation

INTRODUCTION Portopulmonary hypertension (PPH) is an uncommon but serious complication of chronic liver disease. It is accepted to be a poor prognostic factor in the follow-up of patients who have undergone orthotopic liver transplantation (OLT). The presence of severe PPH is accepted as a contraindication to OLT. In this study we sought to identify the prevalence and impact of PPH on the outcome of OLT patients. PATIENTS AND METHODS We retrospectively analyzed the records of 114 adult OLT patients operated on at our institution. A complete transthoracic Doppler echocardiographic examination was performed preoperatively and postoperatively. To identify PPH, patients with Doppler echocardiographically measured systolic pulmonary artery pressure (SPAP) values of >or=30 mm Hg were defined as PPH. We noted the etiology of the liver disease, the postoperative mortality rates, and the pulmonary complications among OLT patients with PPH. RESULTS In 24 patients we detected PPH, a prevalence of 21.1% among patients referred for OLT. Their mean age was 44.0 +/- 13.5 years; 18 patients (75.0%) were males. With regard to the Child classification, 16 (66.7%) were in class C. The mean SPAP was 46.6 +/- 7.6 mm Hg. Compared with preoperative values, a significant decrease in mean SPAP was noted postoperatively; 46.6 +/- 7.6 mm Hg vs 37.8 +/- 15.5 mm Hg (P < .05). Concerning postoperative pulmonary complications, pneumonia developed in 7 (29.2%), pleural effusion in 6 (25%), and respiratory failure and right ventricular failure in 1 (4.2%) subject. Compared with patients with a normal SPAP, the postoperative pulmonary complication rate was higher and the length of hospitalization longer among patients with PPH (P < .05). However, no difference was observed in terms of mortality rates (P > .05). CONCLUSION This study indicated that SPAP decreased among patients with PPH following OLT. Although there was an increase in pulmonary complications, we observed no alteration in mortality rates. Therefore, we suggest that PPH may not be regarded as a contraindication for OLT.

BRONCHIECTASIS-RELATED AMYLOIDOSIS AS A CAUSE OF CHRONIC RENAL FAILURE

Bronchiectasis is defined as acquired and permanent abnormal dilation and destruction of the bronchial walls. Secondary amyloidosis is a disorder characterized by the deposition of amyloid A (AA) in multiple organs and tissues in the body. End-stage renal disease (ESRD) secondary to bronchiectasis-related amyloidosis has only been mentioned in case reports. Little is known about the complications of bronchiectasis-related amyloidosis and the outcomes in patients who develop ESRD due to amyloid deposition in the kidneys. The aim of this study was to identify the clinical characteristics of this patient group, and to report the outcomes of these cases relative to bronchiechtasis type. We assessed the records of 40 patients with AA-type amyloid nephropathy and ESRD who were on hemodialysis (HD) at Baskent University Hospital between 1997 and 2000. The diagnosis of amyloidosis was based on histopathological findings in kidney, rectum, bone marrow, lymph node, thyroid, bladder, liver, and stomach biopsies. Bronchiectasis was diagnosed on the basis of history and findings on physical examination, chest X-ray, and thoracic high-resolution computerized tomography (HRCT). The patients’ records were retrospectively evaluated for cause of secondary amyloidosis, and cases with causes other than bronchiectasis were excluded. Secondary amyloidosis due to bronchiectasis and recurrent pulmonary infection was identified in 40% (16 patients) of the 40 patients. For each of these 16 cases, we recorded patient age, duration of bronchiectasis, duration of HD, amount of lung involvement, and biopsy site(s). The means for age, duration of bronchiectasis, and duration of HD in the 16 patients were 50.6 ± 13.5 years, 22.18 ± 12.02 years (range, 6–42 years), and 30.81 ± 36.94 months (range, 4–144 months), respectively. The most common biopsy site was the rectum (n = 8). Thoracic HRCT revealed cystic bronchiectasis in 8 cases (50%). Four of these 8 patients (25% of the group of 16) died from sepsis within 3-year follow-up period. Two of the four patients who died had bilateral cystic bronchiectasis, and the other two had unilateral cystic bronchiectasis. In the other eight patients in the group, thoracic HRCT showed chronic fibrotic changes in the pulmonary parenchyma and minimal traction bronchiectasis. Four of these patients exhibited apical fibrosis and bronchiectasis (25% of the group of 16), and these radiological findings were considered sequelae of previous tuberculosis infections. In conclusion, chronic respiratory infections and associated bronchiectasis remain a serious problem in Turkey due to insufficient prevention, diagnosis, and treatment. It is important that patients with progressive cystic and diffuse bronchiectasis be followed carefully, as they may develop amyloidosis and ESRD in time. Also, the clinical course in patients with cystic bronchiectasis may be worse than that in other types of bronchiectasis due to complicating pulmonary infections.

Evaluation of liver transplant candidates: A pulmonary perspective.

Chronic liver disease is one of the leading causes of mortality and morbidity in the worldwide adult population. Liver transplant is the gold standard therapy for end-stage liver disease and many patients are on the waiting list for a transplant. A variety of pulmonary disorders are encountered in cirrhotic patients. Pleura, lung parenchyma, and pulmonary vasculature may be affected in these patients. Hypoxemia is relatively common and can be asymptomatic. Hepatopulmonary syndrome should be investigated in hypoxic cirrhotic patients. Gas exchange abnormalities are common and are generally correlated with the severity of liver disease. Both obstructive and restrictive types of airway disease can be present. Abnormal diffusion capacity is the most frequently observed pulmonary function disorder in patients with cirrhosis. Hepatic hydrothorax is another finding which is usually seen in conjunction with, but occasionally without ascites. Portopulmonary hypertension is a complication of long standing liver dysfunction and when severe, is accepted as a containdication to liver transplant. Since respiratory disorders are common and have significant impact on postoperative outcome in patients undergoing liver transplant, a careful preoperative pulmonary assessment is important.

Acute Interstitial Pneumopathy Associated with Docetaxel Hypersensitivity

Background: Acute pulmonary toxicity in cancer patients treated with docetaxel has been reported in previous phase II studies and case reports. Unlike transient pulmonary infiltrates, it is demonstrated that docetaxel-induced interstitial pneumopathy is a severe clinical condition that generally leads to respiratory failure. Case Report: We report a patient with breast cancer who received 2 cycles of docetaxel in 3-week intervals and developed respiratory failure. The clinical, pathologic, and radiographic data supported pulmonary toxicity caused by a hypersensitivity reaction to docetaxel as the most likely etiology. The patient developed the same symptoms and radiological findings after 1 cycle of paclitaxel administration. Unlike other more severe examples in the literature, this patient’s condition did not require mechanical ventilation, and she recovered after corticosteroid treatment. Conclusion: The present case raises the possibility that taxanes, as a group of chemotherapeutic agents, may cause the same type of adverse reaction in the pulmonary parenchyma. The authors recommend that any patient who develops a taxane- induced pulmonary toxic reaction, not be rechallenged or treated with another agent of the same class.

Pulmonary infections in transplant recipients.

PURPOSE OF REVIEW Hematopoietic stem cell as well as solid-organ transplantation is being carried out with increasing frequency throughout the world. Lower respiratory tract infections (LRTIs) remain a common life-threatening complication faced by the transplant recipients. The purpose of this review is to provide up-to-date information on pulmonary infections among the transplant recipients, especially emphasizing the endemicity of microorganisms, epidemiology, work-up of infections, and principles of their management. RECENT FINDINGS A lower respiratory tract infection such as pneumonia is the most frequent of all the infections and is associated with high morbidity and mortality. Factors increasing the risk of pulmonary infections include surgical techniques, immune status, chemoradiotherapy, alloimmune mechanisms between the host and the graft, and the environment. A high degree of suspicion, computed tomography (CT) scan of the chest, and flexible bronchoscopy are required in most to establish the diagnosis. SUMMARY Proper management of LRTI in transplant recipients requires a high degree of suspicion, thorough knowledge of the epidemiology and endemicity of the suspected organisms, CT scan of the chest, and expertise at bronchoscopy. Utmost teamwork among transplant physicians, infectious disease specialist, and bronchoscopist is essential.