Bronchiolitis obliterans organizing pneumonia: a distinct pulmonary complication in cystic fibrosis.

Organizing pneumonia in cystic fibrosis has hitherto been considered a nonspecific reparative process. We report on an adult patient with cystic fibrosis and histologically proven bronchiolitis obliterans organizing pneumonia, who experienced sustained clinical improvement under corticosteroid therapy. This case suggests that bronchiolitis obliterans organizing pneumonia may be a distinct pulmonary complication in cystic fibrosis and improve with specific therapy.

Severe cytomegalovirus-triggered autoimmune hemolytic anemia complicating vertically acquired HIV infection.

The association of acute cytomegalovirus infection with severe autoimmune hemolysis has not yet been reported in patients with HIV infection. The case is described of a 9-month-old infant with congenital HIV-1 infection who presented with severe autoimmune hemolysis and a high cytomegalovirus viral plasma load. Alternative causes of the hemolysis, such as drugs or other infections, were ruled out. After birth and after successful therapy of hemolysis, cytomegalovirus was not detected in the plasma, strongly suggesting a causal relationship between the hemolysis and cytomegalovirus infection. Severe autoimmune hemolysis should thus be considered as a cytomegalovirus-associated complication in HIV infection.

Effect of cisapride on acid gastro-oesophageal reflux during treatment with caffeine.

About 50% of preterm infants and neonates receiving methylxanthines for respiratory stimulation will develop a pathological gastro-oesophageal reflux (GOR) pattern. In the face of potential GOR-related complications the effect of a concomitant treatment with a prokinetic agent, such as cisapride, should be evaluated. In this study 32 formerly preterm infants were studied simultaneously by 24-hour oesophageal pH monitoring and cardio-respirogram before the presumed end of caffeine treatment. In 14 of these infants a reflux index (RI; percentage of recording time) of more than 4% could be detected (pH <4). Ten of them were treated orally with cisapride (0. 2 mg/kg t.i.d.). Data of pH monitoring, cardio-respirogram and caffeine serum concentrations were obtained before and 5 days after introducing cisapride. The RI and the frequency of GOR decreased significantly with cisapride. The steady-state serum concentrations of caffeine were not influenced by cisapride and the extent of periodic breathing remained unchanged. In conclusion, cisapride has a positive influence on GOR parameters during caffeine treatment without impairing the oral bioavailability or therapeutic effect of caffeine.

Pneumonectomy in cystic fibrosis.

A 17-year-old boy and a 12-year-old girl with cystic fibrosis (forced expiratory volume in 1 sec, 36% and 14% of predicted values, respectively) developed severe right-sided lung infections with abscess formations and complete atelectases unresponsive to medical therapy. In both patients, unilateral emergency pneumonectomy resulted in rapid clinical improvement. Despite her severe underlying lung disease, the girl experienced a remarkable increase in quality of life; 2 years after surgery, she died from respiratory failure. The male patient has now survived for 4 years, and lung transplantation still remains a therapeutic option for him. We believe that pneumonectomy is a valuable rescue therapy for patients with cystic fibrosis and intractable unilateral lung infections who are at high risk of dying while waiting for lung transplantation.

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance.

UNLABELLED: Impaired glucose tolerance (IGT) is an increasingly frequent complication of cystic fibrosis (CF). In CF patients, a fast postprandial rise in plasma glucose is typically followed by a delayed but prolonged insulin response. Patients may develop symptoms of both hyper- and hypoglycaemia. The alpha-glucosidase inhibitor, acarbose, delays the hydrolysis and subsequent absorption of ingested carbohydrates. The aim of this study was to investigate the efficacy of acarbose in CF patients with IGT. During a 2-week inpatient period for treatment of Pseudomonas infection, 12 CF patients with IGT were studied in a double-blinded, randomized crossover trial. Each patient received acarbose (50 mg t.i.d.) for 5 days and placebo for 5 days (days 3-8 and days 10-14, respectively). Glucose, insulin and C-peptide responses to a standardized nutritional load were measured at baseline and at the end of each study period (Days 2, 8 and 14). Treatment with acarbose was associated with significant reductions in the mean value, mean peak values and the area under the curve of plasma glucose, insulin and C-peptide, compared to respective baseline values and placebo. Gastro-intestinal disturbances were recorded in 67% of patients during therapy with acarbose. CONCLUSION: Acarbose has a positive therapeutic effect on glucose tolerance in cystic fibrosis patients, as shown by attenuation of postprandial plasma glucose increase and a significant decrease in insulin secretion response. However, acarbose treatment was associated with adverse gastro-intestinal effects that may prevent patients from accepting long-term therapy.

Early versus late dexamethasone treatment in preterm infants at risk for chronic lung disease: a randomized pilot study.

UNLABELLED: Abstract The purpose of this controlled, prospective pilot study was to compare the short-and long-term efficacy of early versus late treatment with dexamethasone (Dex) in preterm infants at risk for chronic lung disease (CLD). Thirty ventilated premature infants with a birth weight < or = 1250 g were randomized to receive Dex either from day 7 or from day 14. Dex was administered over 16 days tapering from 0.5 mg/kg per day to 0.1 mg/kg per day. The infants of the early treatment group could be weaned significantly earlier from the ventilator after 14 days (median; range 9-24) versus 24 days (median; range 8-44) in the late treatment group. The need for supplemental oxygen was shorter if Dex was started early - 24 days (median; range 10-57) versus 40 days (median; range 10-74). Oxygen dependency at 28 days of age was similar between the groups 6 out of 14 infants (42.9%) versus 10 out of 16 patients (62.5%). The long-term efficacy of the two Dex regimens on lung function was evaluated by body plethysmographic measurements made at the age of 3 months. Thoracic gas volume and airway resistance were measured and specific airway conductance calculated. No statistically significant differences between the groups were demonstrated. CONCLUSION: Early dexamethasone treatment led to earlier extubation in our study population, but was not associated with significant advantages regarding oxygen dependency at 28 days of life and pulmonary function test at 3 months of age.

Effects of hyperoxia on oxygen uptake kinetics in cystic fibrosis patients as determined by pseudo-random binary sequence exercise.

Patients with cystic fibrosis (CF) have been shown to exhibit impaired oxygen uptake (VO2) kinetics independent of their physical fitness. This study investigated whether oxygen supplementation improves VO2 kinetics in CF as determined by cycle ergometry at submaximal exercise intensities using a pseudo-random binary sequence exercise test i.e. a simultaneous application of different frequencies of sinusoidal work. The subjects were 9 CF patients and 13 healthy controls (HC) and they exercised while breathing humidified and heated air with a fractional concentration of oxygen in inspired air (F(I)O2) of either 0.21 or 0.40. With a F(I)O2 of 0.21 the respiratory exchange ratio (R) was higher in CF than in HC both at rest (0.91 vs 0.81) and during exercise (0.97 vs 0.89). Oxygen saturation (SO2) was slightly lower in CF. but remained above 90% during exercise (92.7% vs 95.2%). Spectrum analysis revealed that in CF, the amplitude ratio (AR) between V02 and exercise intensity was lower over a wide frequency range (P < 0.05). In addition, CF showed a larger negative phase shift (PS) at lower frequencies (P < 0.005). With a F(I)O2 of 0.40, SO2 increased to about 97% in both groups; while R remained higher in CF (0.92) compared to HC (0.81). In the control group, the O2 supplement raised AR but the VO, kinetics of the CF patients were not significantly affected. In HC the enhanced AR during oxygen supplementation would suggest a cardiopulmonary limitation of VO2 at the onset of submaximal exercise. In CF patients low AR and PS would indicate an attenuated VO2 response attributable to an impaired oxygen utilization in the muscles because the oxygen supplement normalised SO2 but failed to improve R and VO2 kinetics.

Inhaled budesonide in ventilator-dependent preterm infants: a randomized, double-blind pilot study.

The aim of this randomized, double-blind pilot study was to evaluate the short-term efficacy of early inhalation therapy with budesonide in ventilator-dependent preterm infants. The primary outcome variable was the duration of artificial ventilation; secondary outcome variables were the need for supplemental oxygen and the release of several inflammatory mediators in the tracheobronchial aspirate fluid. The infants of the budesonide group could not be weaned earlier from the ventilator. The ventilatory parameters on day 14 of life and the need for supplemental oxygen were similar in both groups. The release of inflammatory mediators was not reduced in the budesonide group. No adverse side effects were observed in either group. In conclusion, aerosolized budesonide failed to demonstrate significant short-term pulmonary improvement in ventilator-dependent preterm infants.

Herpes virus (KSHV) associated Kaposi sarcoma in a 3-year-old child with non-HIV-induced immunodeficiency.

UNLABELLED: A 3-year-old boy of German descent suffered from two episodes of Streptococcus pneumoniae meningitis within 2 months. One month previously, the first skin lesion of Kaposi sarcoma (KS) had been observed behind his right ear. During the following 2 years KS disseminated not only mucocutaneously but also to visceral organs. Immunological evaluation revealed severe lymphocytopenia with reduced helper/suppressor T-cell ratio and impaired humoral immune response to pneumococci. Extensive laboratory tests gave no evidence for known immunocompromising infections. However, recently described DNA sequences from a Kaposi sarcoma-associated herpesvirus (KSHV) could be identified within skin tissue. As chemotherapy failed to stop tumour progression the patient was referred for bone marrow transplantation. Eighteen months later the KS is in remission and the patient in a good general condition. CONCLUSION: The case supports the hypothesis that KSHV is involved in the aetiology of KS. Bone marrow transplantation is possibly a therapeutic option for KS in patients with immunodeficiency not related to human immunodeficiency virus infection.

Central pontine myelinolysis associated with acquired folate depletion.

After long-standing malnutrition a 15-month-old boy with signs of kwashiorkor was admitted in a moribund state with serious hyponatraemic dehydration, hypothermia, somnolence, and signs of a pontine disconnection syndrome. Folic acid levels were below the detection level in the presence of normal cobalamin levels. MRI of the brain showed global volume loss and signal abnormalities on the T2-weighted images suggestive for central pontine myelinolysis (CPM). Brainstem acoustic evoked responses have remained normal. The serious metabolic and nutritional derangements required substitution of folic acid, vitamins and trace elements as well as slow correction of hyponatraemic dehydration with return of the sodium level over a period of four days. This therapeutic regimen resulted in complete neurological recovery. Follow-up MRI documented normalisation of the initial pathologic findings. The hypothesis was put forward linking the pathogenesis of CPM with the combination of folate depletion and superimposed hyponatraemic dehydration. The previously acquired folate depletion could affect normal appositional function of myelin basic protein molecules due to insufficient methylation of arginine in position 107. The subsequent development of intramyelinic edema and CPM will then be triggered by the superimposed hyponatraemic dehydration. The verification of this hypothesis requires further investigations.

Persisting unilateral lung hypoperfusion after resection of a subcarinal bronchogenic cyst.

As a rare malformation with a wide variety of clinical modes of presentation, the bronchogenic cyst remains a diagnostic challenge. We report a case with a subcarinal bronchogenic cyst and stenosis of the left main bronchus presenting as "unilateral hyperlucent lung". Hypoplasia of the ipsilateral pulmonary vascular system persisted after surgical restitution of ventilation and is most likely due to an associated vascular malformation. Alternatively, anatomical fixation of pulmonary reflex vasoconstriction can be discussed.

Increased physiological dead space during exercise after bronchodilation in cystic fibrosis.

Bicycle ergospirometry was performed on 14 patients with cystic fibrosis (CF), for evaluating the effects of salbutamol and theophylline on the ventilatory response to exercise. After 1 week without bronchodilator therapy the patients cycled at 1/3 and 2/3 of their individual maximal working capacity (Wmax). The test was repeated three times after treatment with salbutamol, theophylline, or both drugs, respectively. After the combined therapy, physiological deadspace, ventilation, ventilatory equivalent of oxygen, and end-expiratory oxygen pressure increased significantly during steady state exercise at 1/3 Wmax. Similar, although not statistically significant changes, were observed after monotherapy with salbutamol or theophylline and during exercise at 2/3 Wmax. These effects could not be predicted by any lung function tests at rest or by the Shwachman-Kulczycki score. The results indicate that in some patients with CF bronchodilators can impair lung function during exercise. In conclusion, the effects of medication on exercise performance of patients with CF have to be considered. Especially, the use of bronchodilators requires a careful evaluation of their real benefit in each individual patient.

[Glucose homeostasis in cystic fibrosis. Oral glucose tolerance test in comparison with formula administration]. / Glukosehomöostase bei zystischer Fibrose. Oraler Glukosetoleranztest im Vergleich zu einer Formulabelastung.

BACKGROUND: Glucose tolerance is often impaired in Cystic Fibrosis. The impact of this condition on enteral nutritional support in case of malnourishment remains to be studied. METHOD: In this study the glucose-, C-peptide- and insulin-responses to an OGTT and a standard enteral formula load were investigated in 19 non-diabetic CF-patients. Each test was performed with a carbohydrate load of 1.75 g/kg bodyweight. RESULTS: 11 patients had a normal OGTT (Group I) and 8 had an impaired glucose tolerance (Group II). After the formula load the glucose concentrations were significantly lower than after the OGTT at 30, 60, and 90 min in both groups and at 120 min in group II only. In group II the glucose values exceeded 6.7 mmol/l at 120 min after both OGTT and formula load and were significantly higher than in group I. The food glycaemic index, a parameter for comparison of glucose response to different diets was calculated. It ranged from 30 to 80% in both groups. An increased C-peptide- and insulin-secretion was found in patients with impaired glucose tolerance. CONCLUSIONS: The condition of impaired glucose tolerance must be considered for enteral hyperalimentation of Cystic Fibrosis-patients. The selection of formulas for nutritional support should be based on the calculation of the Food Glycemic Index because of its high interindividual variability.

[Cardiopulmonary capacity in patients with mucoviscidosis. Comparison of ergospirometry findings with clinical and radiological scores]. / Kardiopulmonale Leistungsfähigkeit von Patienten mit Mukoviszidose. Vergleich ergospirometrischer Befunde mit klinischen und radiologischen Scores.

AIM OF STUDY: Shwachman-Kulczycki- and Chrispin-Norman-Scores are widely used scoring systems for CF-patients. Maximum bicycle exercise testing was performed in 15 patients (medium age 13.4 years) to investigate whether clinical and radiographic scores or pulmonary function testing could predict cardiorespiratory fitness. METHODS: A progressive exercise test was used to determine maximum working capacity (Wmax). Prior to exercise testing, lung function and blood gases were investigated. Chest radiographs were scored by an independent radiologist (G.B.) applying the Chrispin-Norman-Score. The Shwachman-Kulczycki-Score was determined by two observers (F.F., H.S.). RESULTS: Chrispin-Norman-Score, Schwachman-Kulczycki-Score, results of lung function testing and blood gas values were significantly correlated to each other. However no significant correlation was found to the degree of exercise limitation. CONCLUSION: Clinical, radiographic scores and lung function testing cannot predict exercise tolerance. Exercise testing is mandatory to evaluate cardio-respiratory fitness in CF-patients.

Exophiala dermatitidis pneumonia in cystic fibrosis.

The chest X-ray film of a girl with cystic fibrosis (CF) showed slowly increasing mottled densities during the 6th and 7th year of her life. Pulmonary symptoms and distress proceeded fast in spite of intensive treatment with antibiotics, corticosteroids, and physiotherapy. Three different fungal organisms were repeatedly cultured from the sputum: Candida albicans, Aspergillus fumigatus, and Exophiala dermatitidis. Antibodies against C. albicans were in the normal range. Candida antigen in blood and antibodies against A. fumigatus were absent. Antibodies against E. dermatitidis were detected by a recently developed indirect immunofluorescence assay. It seems most probable that E. dermatitidis was the causal agent for fungal pneumonia in this case. Under therapy with amphotericin B and flucytosine the clinical course and radiological appearance improved but definitive eradication of E. dermatitidis was only achieved after treatment with itraconazole. The isolation of this fungus from the sputum of a CF patient is reported for the first time. The significance of fungal infections in CF is discussed.

[Tuberculosis and cystic fibrosis]. / Tuberkulose und Cystische Fibrose.

Mycobacterial infections are rarely reported in Cystic Fibrosis patients although they quite often develop predisposing risk factors such as underweight, secondary diabetes mellitus and chronic inflammatory pulmonary disease. Furthermore glucocorticoid therapy is mandatory in some patients. CF heterozygotes are said to have a selective advantage due to an increased host resistance against Mycobacterium tuberculosis. In this survey 1926 CF patients were investigated for the incidence of tuberculin conversion and manifest infection with mycobacterium tuberculosis in the Federal Republic of Germany (FRG). The results do not support the hypothesis of increased host resistance nor do they show any evidence of a higher risk for tuberculosis in CF. Implications for prophylactic, diagnostic and therapeutic measures are discussed in accordance to the recent epidemiologic data of tuberculosis in the FRG.

Long-term fungal cultures from sputum of patients with cystic fibrosis.

Mycological examination of sputum from 121 patients with cystic fibrosis by means of long-term cultures (4 weeks) revealed the occurrence of Candida albicans in low quantities in 70%, Aspergillus fumigatus in 30%, and Exophiala/Wangiella dermatitidis in 9% of the examined patients. A. fumigatus frequently causes the development of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. The predisposing factors for colonization with the otherwise seldom found fungus E. dermatitidis in these patients and the consequences of these findings are discussed. In conclusion, long-term fungal cultures are advocated for specimens from CF patients.