Evaluation of pulmonary infections in solid organ transplant patients: 12 years of experience.

BACKGROUND: Recipients of solid organ transplants (SOTs) are at higher risk to develop pulmonary infections (PIs) owing to their immunocompromised state. Flexible bronchoscopy (FB) is frequently performed to diagnose nature of these infections. The aim of 12-year review was to evaluate the demographic characteristics of SOT recipients with PIs and to study diagnostic utility of FB in this group of patients. METHODS: Medical records of patients who underwent SOT as well as FB between 2000 and 2012 were retrospectively reviewed. Patients' demographics, type of transplantation, primary diagnoses, thoracic computed tomography (CT) findings, total blood count and chemistry, indication for FB, FB results, specimen culture results, and suspected and final diagnoses were all recorded. If the bronchoscopy findings altered medical management and produced improvement in PI, the procedure was considered diagnostic. RESULTS: Ninety of 998 liver, heart, or kidney transplant recipients underwent FB (73 renal, 16 liver, and 1 heart; mean age, 42.3 ± 12.1 years) during the study period. CT findings were as follows: Consolidation (49.4%), lymphadenopathy (3.4%), nodular infiltrates (5.6%), and cavitary lesion (1.1%). FB was unremarkable in 29, but showed increased secretions in 33 patients (36.7%), chronic mucosal changes in 9 (10%), edema in 7 (7.8%), mucosal plaque in 7 (7.8%), friable mucosa in 3 (3.3%), and endobronchial lesion in 2 (2.2%). A total of 29 bronchial washings (BW; 32.6%) and 10 bronchoalveolar lavages (BAL; 11.2%) were performed. PI was diagnosed in 82% of the patients (n = 73). In 32 patients (36%), micro-organism growth was observed on either BW or BAL. Mycobacterium tuberculosis was detected in 6 (6.7%), Staphylococcus aureus in 4 (4.4%), Moraxella catharralis in 4 (4.4%), Candida albicans in 6 (6.7%), Klebsiella pneumonia in 2 (2.2%), Escherichia coli in 2 (2.2%), Streptococcus pneumoni in 2 (2.2%), Stenotrofomonas maltofilia in 1 (1.1%), Aspergillus fumigatus in 4 (4.5%), and Pseudomonas aeruginosa in 1 (1.1%). Final diagnosis was established by FB (n = 33) with a diagnostic yield of 36%. No significant finding was observed between the type of the transplant and the culture results (P > .05). CONCLUSION: Suspected PI is the most common indication for FB in SOT recipients. It may identify the causative organism in >30% of patients. Tuberculosis was found to be the most frequent agent, which is not surprising from such an endemic area. Bacteria were more common than fungal or viral micro-organisms. FB should be considered in SOT recipients presenting with lung infiltrates and suspected to have PI.

Association between "Malnutrition Inflammation Score" and airway obstruction in patients awaiting renal transplantation: a preliminary study.

BACKGROUND: A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD) who are undergoing maintenance hemodialysis (MHD). "Malnutrition Inflammation Score" (MIS) is a comprehensive scoring system that measures nutrition and inflammation in MHD patients. Inflammation and malnutrition are important risk factors in ESRD patients with pulmonary diseases. The aim of the study was to determine if pulmonary dysfunction, as assessed by airway obstruction, was associated with malnutrition and inflammatory factors in ESRD patients awaiting renal transplantation (RT). METHODS: Patients with ESRD who were on MHD and had pulmonary function tests (PFTs) were retrospectively enrolled in the study. Patients' renal function tests, albumin, C-reactive protein (CRP) levels, white blood cell count, and PFTs (forced expiratory flow rate in one second [FEV1], forced vital capacity [FVC], forced expiratory flow at 25%-75% [FEF25%-75%], and peak expiratory flow [PEF]) were recorded. MIS was calculated for each patient. RESULTS: A total of 81 patients (male=54; mean age: 50.6±13 years) were recruited. Mean body mass index (BMI) was 22.5±4.4 kg/m2, mean MIS was 7.1±3.3, mean CRP level was 24.9±48.1 mg/L, mean FEV1% was 94±22, and mean FEF25%-75% was found to be 72.3±30.3. Mean duration of MHD was 10.5±5.2 years. There was a negative correlation between FEV1, FVC, FEF25%- 75%, PEF, and MIS (r=-0.3, P=.00; r=-0.32, P=.00; r=-0.22, P=.04; r=-0.30, P=.00, respectively). Nevertheless, FEV1 values significantly correlated with BMI (P=.03) and the MIS (P=.00). CONCLUSION: Impaired pulmonary function could be a marker of inflammation and malnutrition in ESRD patients awaiting RT. Prospective studies are needed to investigate the relationship between pulmonary function, inflammation, and malnutrition in larger populations of ESRD patients. Treatment geared towards malnutrition and inflammation markers may help maintain PFTs within normal range, which may prevent pulmonary complications following RT.

Diagnostic utility of flexible bronchoscopy in recipients of solid organ transplants.

BACKGROUND: Solid organ transplant (SOT) recipients are prone to develop pulmonary complications (PC) due to their immunocompromised state. Flexible bronchoscopy (FB) is frequently performed to diagnose the nature of these complications. The aim of this study was to evaluate the diagnostic utility of FB in SOT recipients with suspected PC. METHOD: We examined the medical records of patients who underwent FB between 2000 and 2010; patients who received SOT were included patient demographics, transplantation type, primary diagnoses, thorax computed tomography results, total blood count and chemistries, immunosuppressant therapies, indication, results, specimen cultures, as well as suspected and final diagnoses were recorded. RESULTS: Among 1368 either liver or kidney transplant recipients 61 subjects including 49 male patients of overall mean age 42.8±12 years underwent FB. FB was performed for lung infiltrates (n=42), lung nodules (n=2), atelectasis (n=1), bronchopleural fistula (n=1), stridor (n=1), mediastinal lymphadenopathy (n=2), pleural effusion (n=1), fever (n=9), and/or hemoptysis (n=2). FB was unremarkable in 17. Other findings were as follows: increased secretions (n=24), chronic mucosal changes (n=7), endobronchial lesion (n=1), edematous mucosa (n=3), submucosal narrowing (n=1), necrotic plaque (n=2), hemorrhage (n=2), tracheal stenosis (n=1), and/or friable mucosa (n=3). We performed bronchial washings (n=56) and/or bronchoalveolar lavage (n=5). In 24 patients the microorganisms were Mycobacterium tuberculosis, Staphylococcus aureus, Moraxella catharralis, Candida albicans, Klebsiella pneumonia, Escherichia coli, Streptococcus pneumonia, Stenotrofomonas maltofilia, Aspergillus fumigatus, and Pseudomonas aerigunosa. In 34 patients a final diagnosis was established using FB (diagnostic yield, 55.7%). Thirty-one patients had received tacrolimus (10.5±5.3 ng/ng/mL); 22 cyclosporine (187.1±79.3 ng/mL); and 8, sirolimus (6.2±2.2 ng/mL). No significant difference was observed between high versus low drug levels and the culture results (P>.05). CONCLUSION: Suspected pulmonary infection is the most common indication for FB in SOT recipients. It may identify the causative organism in more than 30% of patients and should be considered in the presence of a lung infection.

Pulmonary complications in renal recipients after transplantation.

BACKGROUND: Renal transplantation is the most common type of solid organ transplantation. Recipients are susceptible to a variety of pulmonary complications, in particular during intense immunosuppression therapy. OBJECTIVE: To evaluate pulmonary complications during the first year after renal transplantation. MATERIALS AND METHODS: Medical records were reviewed retrospectively for all patients who underwent renal transplantation between 2007 and 2010. Data pertinent to pulmonary complications were obtained including patient demographics, findings at chest radiography and pulmonary function testing, concentrations of C-reactive protein and albumin, and white blood cell count. RESULTS: The study included 136 patients (71.3% men), with mean (SD) age of 36.3 (12.2) years. The most frequently prescribed immunosuppression therapy included prednisolone plus cyclosporine, tacrolimus, or rapamycin. Fifteen patients developed complications during the first year after surgery including respiratory infections in 12 (80%), namely, bacterial pneumonia in 10 (66.6%), and tuberculosis (caused by Mycobacterium tuberculosis) in 2 (33.3%). Pneumonia developed within the first 5 months after transplantation in 6 patients, and tuberculosis after the third month. Microbiologic agents were detected in 3 of the 6 patients (20%), and empyema, postoperative atelectasis, and pulmonary embolism, respectively, in the other 3 patients. No association was observed between complications and baseline pulmonary function test results. C-reactive protein concentration was significantly increased in patients with pulmonary complications. No invasive procedures were performed to diagnose complications, all of which resolved with appropriate treatment. CONCLUSION: Pulmonary infections are a primary complication in renal transplant recipients, and are observed most frequently in the first 6 months after surgery. Immunosuppression therapy is the most likely cause of these complications, and rigorous monitoring of drug concentrations is essential. An invasive diagnostic approach may not always be necessary to determine the early specific therapy.

Factors affecting morbidity and mortality in flail chest: comparison of anterior and lateral location.

OBJECTIVE: Flail chest is most often accompanied by significant underlying pulmonary parenchymal injuries and may constitute a life-threatening thoracic injury. In this study we evaluated the treatment modalities for flail chest depending on the effect of trauma localization on mortality and morbidity. METHODS: Between 2003 and 2008, 23 patients (20 males/3 females) were treated for flail chest. Location of the trauma in the chest wall, mechanical ventilation support, prognosis and injury severity score (ISS) were recorded for all patients. Mechanical ventilation support was given in 14 patients (60.8 %), and 12 of these 14 patients required subsequent tracheostomy. Internal fixation was used in 3 patients. RESULTS: The major cause of flail chest was a car crash in 18 of 23 patients (76 %). Median ISS was 62.8 for all patients. The patients with flail chest who had bilateral costochondral separation (anterior chest location) (group I, n = 10) had a significantly higher ISS than those with single-side posterolateral flail chest (group II, n = 13; ISS: 70/55; P = 0.02). The need for mechanical ventilation support was also higher in the group with bilateral costochondral separation. Morbidity was higher in group I than in group II ( P = 0.198), and mortality was also significantly higher in group I ( P = 0.08). Patients with a cranial trauma and flail chest had a higher mortality (19 %) than patients with only flail chest (no mortality). The mean ISS was 75 for patients with cranial trauma and flail chest and 55.7 ( P = 0.001) for patients with only flail chest. Sepsis and subarachnoid bleeding were the major causes of mortality. The mean ISS was 54.5 for patients under the age of 55 (n = 14) whereas it was 69.4 in those aged 55 and over (n = 9; P = 0.034). Mortality in the older group was also higher (33 % versus 7 %; P = 0.02). CONCLUSION: Early intubation and mechanical ventilation is of paramount importance in patients with flail chest. However, prolonged mechanical ventilation is associated with a poor outcome. Tracheotomy and frequent flexible bronchoscopy are an effective pulmonary toilet. Advanced age was a major risk factor for flail chest trauma mortality, together with the severity of the injury. When cranial trauma was accompanied by flail chest, mortality and morbidity rates increased. Bilateral costochondral separation also increased the risk of morbidity and the need for mechanical ventilation in patients with flail chest.

Bioassay-guided isolation of kaempferol-3-O-beta-D-galactoside with anti-inflammatory and antinociceptive activity from the aerial part of Calluna vulgaris L.

Calluna vulgaris L. (Ericaceae) is used for the treatment of various inflammatory ailments in traditional medicines. In order to evaluate this ethnobotanical information, its anti-inflammatory and antinociceptive activities were studied using in vivo experimental models in mice. The ethanolic extract of the plant was first fractionated into five extracts; namely, n-hexane, chloroform, ethyl acetate (EtOAc), n-butanol, and water fractions. Among them, the EtOAc Fr. was found to be the most effective and was further subjected to bioassay-guided fractionation and isolation procedures. After successive column chromatography applications, on Sephadex LH-20 and silica gel, a component, which is responsible for the above-mentioned activities of this species of Turkish origin, was isolated and its structure was elucidated as kaempferol-3-O-beta-D-galactoside, a common flavonol derivative by means of spectral techniques.

Bioassay-guided evaluation of anti-inflammatory and antinociceptive activities of pistachio, Pistacia vera L.

The ethanolic and aqueous extracts prepared from different parts of Pistacia vera L. (Anacardiaceae) as well as its oleoresin were evaluated for their in vivo anti-inflammatory and antinociceptive activities. Among the extracts screened, only the oleoresin was shown to possess a marked anti-inflammatory activity against carrageenan-induced hind paw edema model in mice without inducing any gastric damage at both 250 and 500 mg/kg doses whereas the rest of the extracts were totally inactive. While the oleoresin was found to display significant antinociceptive activity at 500 mg/kg dose, the ethanolic and aqueous extracts belonging to fruit, leaf, branch and peduncle of Pistacia vera did not exhibit any noticeable antinociception in p-benzoquinone-induced abdominal contractions in mice. Fractionation of the oleoresin indicated the n-hexane fraction to be active, which further led to recognition of some monoterpenes, mainly alpha-pinene (77.5%) by capillary gas chromatography-mass spectrometry (GC-MS) as well as the oleoresin itself. alpha-Pinene was also assessed for its antinociceptive and anti-inflammatory activities in the same manner and exerted a moderate anti-inflammatory effect at 500 mg/kg dose.

Synthesis and analgesic and antiinflammatory activity of methyl 6-substituted-3(2h)-pyridazinone-2-ylacetate derivatives.

A series of methyl 6-substituted-3(2H)-pyridazinone-2-ylacetates 9 were synthesized and their analgesic and anti-inflammatory effects were evaluated in the phenylbenzoquinone-induced writhing test (PBQ test) and carrageenan-induced paw edema method, respectively. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. Methyl 6-(4-(4-fluorophenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9e was found to be more active than acetylsalicylic acid (ASA). Methyl 6-(4-(2-ethoxyphenyl)piperazine)-3(2H)-pyridazinone-2-ylacetate 9c has shown an anti-inflammatory activity as compared to the standard compound indometacin at the carrageenan-induced paw edema method.A significant dependence of the anti-inflammatory effect on the substituents has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at the position 6 of the 3(2H)-pyridazinone system influences analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and (1)H-NMR spectra and elemental analysis.

Clues for the differential diagnosis of hypersensitivity pneumonitis as an expectant variant of diffuse parenchymal lung disease.

Hypersensitivity pneumonitis, also called extrinsic allergic alveolitis, a type of diffuse parenchymal lung disease (DPLD), is an immunologically mediated pulmonary disease induced by inhalation of various antigens. As data on the frequency of hypersensitivity pneumonitis are lacking in Turkey, a retrospective analyses was performed in 43 patients with DPLD, followed up over seven years. The objective was to discover cases fulfilling the diagnostic criteria for hypersensitivity pneumonitis, to determine the frequency and/or the new characteristics of the disease, and to pick up clues for differentiating it from other DPLDs. The four subjects with hypersensitivity pneumonitis (9%) who lived in an urban area were studied in detail. The most common symptoms were dry cough and dyspnoea. According to the symptom duration, clinical features, radiological and pathological findings, three were diagnosed with chronic and one with subacute hypersensitivity pneumonitis. Patients with hypersensitivity pneumonitis and those with DPLD were compared by means of age, sex, smoking status, symptom duration, haematology, erythrocyte sedimentation rate, peripheral cell count, spirometric parameters, blood gases, and diffusion capacity. No statistically significant difference was detected in these parameters except for forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). In conclusion, patients with a history of antigen exposure, with mild symptoms such as dry cough and dyspnoea, and who have diffuse interstitial lung involvement on radiology should be carefully evaluated for hypersensitivity pneumonitis. Moreover, among other DPLDs, stable FEV(1) or FVC values may be the clues for establishing the diagnosis of hypersensitivity pneumonitis. However, further studies are needed in larger series of patients.