cardio-pulmonary study on thalassemic children: relation to oxidant antioxidant balance and iron overload

beta-Thalassemia major is a common inherited disorder of hemoglobin synthesis in which iron overloading from regular blood transfusions results in organ dysfunction. Heart and liver dysfunction in thalassemia have been extensively-studied owing to their early effect on survival. Pulmonary dysfunction on the other hand is one of the least understood complications of beta-thalassemia major and represents one of the least studied complications in thalassemic patients. The aim of this study was to define the spirometric pattern and the possible causes of lung impairment in thalassemic patients. The study included 39 thalassemic patients [19 females and 20 males], with an age range from 8 to 16 years. Eighteen controls of matched age and sex were included in the study. A complete history was taken and a thorough physical examination was performed. In addition, the following investigations were done before blood trans fusion: Hb, serum ferritin level, AST, ALT, erythrocytic thiobarbituric acid reactive substance [TBARS], super oxide dysmutase [SOD]'glutathione peroxidase [GPx], serum TBARS, SOD, glutathione [GSH], and vitamins A, C and E. Echocardiography was also done for all patients, the day before blood transfusion. Pulmonary function testing and arterial blood gases were performed prior to blood transfusion and 24 hours after blood transfusion. Restrictive lung pattern was predominant in beta-thalassemia major patients. This was manifested by a significantly lower FVC and a significantly higher FEV1/FVC in the studied patients than the controls. FVC carried significant negative correlation with ferritin. Patients had significantly higher values of TBARS and significantly lower values of serum SOD, GSH and the erythrocytic SOD and GPx and vitamins [E, A and C]. FVC carried significantly negative correlation with TBARS and significantly positive correlations with erythrocytic SOD, GPx, vitamins A and E. LVESD and LVEDD were significantly higher in the studied patients than the controls and both correlated negatively with FVC. EF, FS and PAT were significantly lower in the studied patients. EF and FAC correlated positively with FVC. L VESD and LVEDD correlated positively with ferritin and TBARS but negatively with GPx. restrictive lung disease was found to be the predominant pulmonary dysfunction in thalassemia major patients. This seems to be related to ferritin level, and might reflect the role of iron deposition and accumulation in the pathogenesis of pulmonary disease in thalassemia major. The restrictive pattern may also result from excess oxidative damage to the alveolar tissue or from cardiac changes that occurred in these patients. Accurate and early evaluation as well as follow up of pulmonary function and of bronchial reactivity is advisable for all patients with TM. Initial and follow up of cardiac performance in patients with thalassemia major is also important as it has a great impact on pulmonary functions in these patients. An ultimate goal in the management of thalassemia major is to design and try a combination of oral antioxidants and oral iron chelator to achieve good patient's compliance with the ease of administration for such patients who are living on repeated blood transfusion and hospital admission

Pulmonary dysfunctions in end stage chronic renal failure children on regular hemodialysis; possible risk factors

Lung and kidney functions are intimately related in both health and disease. In renal failure respiratory changes help to mitigate the systemic effects of renal acid-base disturbances. Changes in the function of the respiratory system are among the frequent complications of renal impairment. Alteration in the respiratory drive, mechanics, muscle function, lung volumes, gas exchange and hemodynamics are frequent and could occur in the lungs without obvious pulmonary symptoms. Their effects could be the way to pulmonary functional disorders. Patients with chronic renal failure treated with hemodialysis may exhibit various changes in ventilation and gas exchange. Moreover, hemodialysis and peritoneal dialysis may have their own impact on the respiratory functions. The main objectives of this work were to assess the pulmonary functions and arterial blood gases as well as assessment of echocardiographic changes in a group of children with chronic renal failure undergoing regular hemodialysis. We also aimed to explore possible risk factors that make these children more liable to disturbed pulmonary function. The study included 19 patients with CRF on regular hemodialysis during the period from January to March 2005. Their ages ranged from 8-17 years [mean 13.63 +/- 2.65]. They were 12 males and 7 females. These patients were attending the pediatric nephrology unit in Assiut University Hospital. The duration of dialysis varied from 1-5 years. Patients with known or recent cardiac, infectious, inflammatory or pulmonary diseases were excluded from the study, They were classified according to the duration of dialysis into two groups. Group [1]: 8 CRF children with duration of dialysis<3 years and Group [2]: 11 CRF children with duration of dialysis >/= 3 years, Fifteen apparently healthy children of matchable age, and sex were included as control group. All subjects had full clinical assessment including body weight, height, wt/ht ratio and full examination including: pulse, blood pressure measurement, chest and cardiac examination. The following investigations were also done: complete blood picture, total serum protein, albumin, urea, creatinine, calcium, phosphorus, and arterial blood gases [before and after a hemodialysis session]. Posteroanterior and lateral chest X-ray and echocardiographic examination. Spirometry was performed at the chest department of Assiut University hospital using sensor Medics [IBM] apparatus. The following parameters were obtained: Forced vital capacity [FVC]; Forced expiratory volume in one second [FEV1]; FEVI/FVC ratio; and Peak expiratory flow rate [PEFR]. Out of the studied patients, 15.79%had pulmonary venous congestion while 10.52%had pleural effusions. On the other hand 15.79%had pericardial effusion and a similar percent had cardiomegaly. Cases as a whole and also both subgroups [A and B] showed significantly lower mean levels of wt/ht ratio, Hb, albumin, Ca, and FS but significantly higher mean levels of systolic blood pressure, blood urea, creatinine, P, LVESD, LVEDD, and indexed LVM than controls. Cases as a whole showed significantly lower mean levels of FVC, FEV1 and PEFR than controls. Cases in group B showed significantly lower mean level of FVC and FEVI and PEFR than controls. Analysis of blood gases showed that cases as a whole and also both groups [A and B] had significantly lower mean levels of pH and HCO3 and base excess than controls. Furthermore both groups showed significantly lower PCO2 before and after a HD session. FVC, FEV1 and PEFR correlated positively with each of wt/ratio ratio, Hb, albumin, Ca and FS and negatively with the duration of the dialysis, creatinine, P, and indexed LVM. Restrictive pattern of pulmonary dysfunctions is frequent in ESCRF patients. Structural and functional cardiac abnormalities are very important among the many predisposing factors for pulmonary function disturbances. Other factors such as malnutrition, hypocalcemia, hyperphosphatemia and anemia may also affect the pulmonary functions indirectly through cardiac affection. Uremic toxins are important factors for both system dysfunctions and the longer the duration of the disease, the more are the disturbances of the pulmonary functions. Low PCO[2] in uremic patients may be a trial by the respiratory system to compensate for acidosis by CO[2] wash in order to elevate the pH to near normal. This is very important since the possible noxious effect of overcorrection of acidosis may lead to alkalosis in such patients who are liable to be alkalosis after dialysis. Although standard treatment of malnutrition in CRF, include measures such as early and adequate dialysis, nutritional counseling, oral protein and amino acid supplements, these interventions cannot restore the nutritional status in all malnourished uremic patients. Adequate management of anemia is critically needed for breaking the cycle connecting renal failure, anemia and cardiac disease [all are predisposing factors for pulmonary dysfunctions]. Adequate management of the cardiac problems as well as appropriate monitoring and follow up is necessary to ameliorate the effects on the lungs and may prevent or delay the occurrence of pulmonary dysfunctions. Hemodialysis itself has its own impact on various organs. This points to the importance of renal transplantation as a better therapeutic alternative particularly in children

Right and left ventricular dysfunction and interaction in respiratory critically ill patients

This study was designed to determine the incidence of right ventricular [RV] and left ventricular [LV] dysfunctions and to relate the findings to possible mechanisms of interdependence between right and left ventricles during acute respiratory failure [ARF] in patients with chronic obstructive lung diseases [COLDs]. 58 hospitalized patients underwent pulmonary function tests and arterial blood gases. An echo-Doppler examination was performed for patients and 20-healthy subjects as control group to measure RV and LV end-diastolic and end-systolic diameters; RV and LV ejection fraction [EF], transmitral early [E] and late [A] peak flow velocities and their ratio [E/A]; isovolumic relaxation time [IRT]; trans-tricuspid early [E1] and late [A1] peak flow velocities and their ratio [E1/A1] and estimation of pulmonary artery pressure [PAP] by acceleration time [ACT] of the pulmonary systolic flow and tricuspid regurgitation [TR] jet velocity. The data showed dilated RV in 80% [50/58]; mild TR in 64% [37/58]; RV systolic dysfunction [EF<45%] in 28% [16/58] and RV diastolic dysfunction [decreased E1/A1 ratio] in 53% [31/58] of patients. On the other hand, LV systolic dysfunction [EF<45%] was found in 16% [9/58] of patients while LV diastolic dysfunction [low E, low E/A ratio and high IRT] in 72% [42/58] of patients. A linear regression analysis revealed that low E and low E/A ratio were significantly correlated with RV size [p<0.01 and p<0.05, respectively], while low E/A ratio and prolonged IRT were significantly correlated with PAP [p<0.05 and p<0.001, respectively]. No significant correlations were found between LV and RV dysfunctions or respiratory functional parameters. In conclusion, the prevalence of RV and LV dysfunctions is high in patients with ARF and LV dysfunction appears to be closely related to the RV size and the level of pulmonary hypertension