Allergen-specific IgE to food molecular components and age: From early childhood to adulthood.

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time with growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4, rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method. Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age until young adulthood and then decreased. A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component tended to increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing), and then to decrease over time. However, the pattern is significantly dependent on each single tested food. CONCLUSIONS: Allergen-specific IgE production to food molecular components tend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.

Intraoperative bronchoscopy for bronchial carcinoid parenchymal-sparing resection: a pediatric case report.

Bronchial carcinoid tumors are the most common primary pulmonary neoplasm in the pediatric population. The widely accepted treatment for carcinoid tumors is surgical, specifically aiming at being as much as conservative on lung parenchyma, while the entire tumor is resected. A brief case is described, highlighting the importance and advantages of a surgical and endoscopic combined approach.

Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is characterised by recurrent infections of the upper respiratory airways (nose, bronchi, and frontal sinuses) and randomisation of left-right body asymmetry. To date, PCD is mainly described with autosomal recessive inheritance and mutations have been found in five genes: the dynein arm protein subunits DNAI1, DNAH5 and DNAH11, the kinase TXNDC3, and the X-linked retinitis pigmentosa GTPase regulator RPGR. METHODS: We screened 89 unrelated individuals with PCD for mutations in the coding and splice site regions of the gene DNAH5 by denaturing high performance liquid chromatography (DHPLC) and sequencing. Patients were mainly of European origin and were recruited without any phenotypic preselection. RESULTS: We identified 18 novel (nonsense, splicing, small deletion and missense) and six previously described mutations. Interestingly, these DNAH5 mutations were mainly associated with outer + inner dyneins arm ultrastructural defects (50%). CONCLUSION: Overall, mutations on both alleles of DNAH5 were identified in 15% of our clinically heterogeneous cohort of patients. Although genetic alterations remain to be identified in most patients, DNAH5 is to date the main PCD gene.

Removal of carbamazepine, diclofenac and trimethoprim by solar driven advanced oxidation processes in a compound triangular collector based reactor: A comparison between homogeneous and heterogeneous processes.

Contaminants of emerging concern (including pharmaceuticals) are not effectively removed by municipal wastewater treatment plants (WWTPs), so particular concern is related to agricultural wastewater reuse due to their possible uptake in crops irrigated with WWTPs effluents. Advanced oxidation processes (AOPs) and solar AOPs have been demonstrated to effectively remove pharmaceuticals from different aqueous matrices. In this study, an heterogeneous photocatalytic process using powdered nitrogen-doped TiO2 immobilized on polystyrene spheres (sunlight/N-TiO2) was compared to the benchmark homogenous AOP sunlight/H2O2 in a compound triangular collector reactor, to evaluate the degradation of three pharmaceuticals (carbamazepine (CBZ), diclofenac (DCF), trimethoprim (TMP)) in water. The degradation of the contaminants by sunlight and sunlight-AOPs well fit the pseudo-first order kinetic model (but for TMP under sunlight). High removal efficiency by solar photolysis was observed for DCF (up to 100%, half-life sunlight cumulative energy QS,1/2 = 2 kJ L-1, half-life time t1/2 = 32 min), while CBZ (32%, QS,1/2 = 28 kJ L-1, t1/2 = 385 min) and TMP (5% removal after 300 min) removal was poor. The degradation rate of CBZ, TMP and DCF was found to be slower during sunlight/H2O2 (QS,1/2 = 5 kJ L-1, t1/2 = 77 min; QS,1/2 = 20 kJ L-1, t1/2 = 128 min; QS,1/2 = 4 kJ L-1, t1/2 = 27 min, respectively) compared to sunlight/N-TiO2 (QS,1/2 = 4 kJ L-1, t1/2 = 55 min; QS,1/2 = 3 kJ L-1, t1/2 = 42 min; QS,1/2 = 2 kJ L-1, t1/2 = 25 min, respectively). These results are promising in terms of solar technology upscale because the faster degradation kinetics observed for sunlight/N-TiO2 process would result in smaller treatment volume, thus possibly perspective compensating the cost of the photocatalyst.

Ag modified ZnS for photocatalytic water pollutants degradation: Influence of metal loading and preparation method.

In this paper, the photocatalytic degradation of organic pollutants was investigated using Ag/ZnS nanoparticles at different noble metal loadings. The photocatalysts were prepared at room temperature by two different methods: photodeposition and chemical reduction. The obtained samples were characterized by Specific surface area measurement, X-ray photoelectron spectroscopy, X-ray Powder diffraction, ultraviolet-visible diffuse reflectance and Raman spectroscopy. The X-ray photoelectron spectroscopy spectra showed that Ag is present on ZnS surface as intermediate state between nanostructured Ag0 and Ag2O. Moreover, the addition of silver caused a significant change of the absorption spectrum of bare ZnS, resulting in higher absorbance in the visible region, due to the Ag surface plasmon band. Methylene blue (MB) was used to evaluate the photocatalytic activity of the prepared samples. The best photocatalytic activity was observed using the sample at 0.1 wt% Ag loading prepared by chemical reduction method. In particular, the almost complete MB degradation was achieved using UV-LEDs as light sources and 6 g L-1 of catalyst dosage. Finally, the optimized photocatalyst was also effective in the degradation of phenol in aqueous solution under UV irradiation.

Spontaneous production of transforming growth factor-beta 2 by primary cultures of bronchial epithelial cells. Effects on cell behavior in vitro.

The ability of airway epithelial cells to produce transforming growth factor-beta (TGF-beta) may be an important mechanism for the control of growth, differentiation, and repair of the airway epithelium. To determine whether airway epithelial cells are capable of producing TGF-beta, we examined primary cultures of bovine bronchial epithelial cells. Using a bioassay, TGF-beta activity was detected readily in media conditioned by bovine bronchial epithelial cells. Neutralizing antisera to TGF-beta 1 and TGF-beta 2 were used to demonstrate that the majority of the activity was of the TGF-beta 2 isoform. Interestingly, some of the TGF-beta activity was present in the conditioned media as "active" TGF-beta, not requiring acid activation. The production of TGF-beta was variable, depending on cell density and the presence of retinoic acid. The presence of endogenously produced active TGF-beta in the culture media was shown to modulate the behavior of the cell cultures as evidenced by the effects of TGF-beta-neutralizing antisera on cell size and fibronectin production. Our results suggest that active TGF-beta produced by airway epithelial cells may function in an autocrine or paracrine manner to modulate epithelial cell behavior.

Following association to the membrane, human erythrocyte procalpain is converted and released as fully active calpain.

When exposed to inside-out human erythrocyte vesicles, in the presence of micromolar Ca2+, the 80 kDa catalytic subunit of procalpain is processed through three successive and sequential steps. These include binding to the cytosolic surface of the membrane, followed by a very rapid conversion into the 75 kDa active subunit, and ultimately by spontaneous and complete release of this active proteinase form. Binding to the membranes is competitively inhibited by the endogenous natural inhibitor through the formation of the proteinase-inhibitor complex, in which form the 80 kDa subunit can no longer be associated to the membranes. Calcium ions and the natural endogenous inhibitor appear to be crucially involved in the modulation of this novel membrane-bound mediated activation of human red cell procalpain.

European multicenter survey on the laparoscopic treatment of gastroesophageal reflux in patients aged less than 12 months with supraesophageal symptoms.

BACKGROUND: This multicenter survey includes neonates and infants who underwent surgery for primary gastroesophageal reflux (GER) who presented with supraesophageal symptoms of unknown origin with a minimum of 12 months postoperative follow-up. METHODS: A total of 726 patients underwent GER surgery in 10 European Centers in the period 1998-2002. Respiratory symptoms were present in 204 patients (28%); 135 patients (17%) had surgery under 1 year of age, and 46 of them (6.3%) because of respiratory symptoms. Surgery was performed without any previous medical treatment in 10 cases (21%). The type of procedure included 37 complete 360 degrees wraps (80%) (Nissen, 12, and Rossetti, 25) and nine partial wraps (20%) (Thal five, Lortat Jacob one, Toupet one, others two). Gastrostomy was associated in 17 cases (37%) (6 PEG and 11 modified Stamm). No gastric emptying procedures were recorded. RESULTS: No major intraoperative complications were reported. Six patients developed complications (13%) and a redo operation was performed in three (6.5%). Respiratory outcome after antireflux surgery was good in 35 patients (76%) and fair with significantly improved respiratory symptoms in 11 (24%). CONCLUSIONS: This multicenter survey underlines that GER has to be suspected and aggressively treated in infants with difficult-to-treat supraesophageal symptoms, and also in high-risk cases, in order to prevent major complications.

Insensitivity of volume-sensitive chloride currents to chromones in human airway epithelial cells.

Chromones (sodium cromoglycate and sodium nedocromil) block cell swelling-activated Cl- channels in NIH-3T3 fibroblasts and endothelial cells. This has led to hypothesize that cell volume regulation might be involved in asthma pathogenesis. Using whole-cell patch-clamp experiments, we studied the effect of chromones on volume-sensitive Cl- currents in transformed human tracheal epithelial cells (9HTEo-) and in primary cultures of human bronchial epithelial cells (BE). Cl- currents activated by hypotonic shock were poorly blocked by extracellular nedocromil or cromoglycate. The block was voltage-dependent since it was observed only at positive membrane potentials. At the concentration of 5 mM, the current inhibition by both chromones at +80 mV was about 40% for 9HTEo- and only 20% for BE. Intracellular application of chromones elicited a voltage-independent inhibition in 9HTEo- cells. Under this condition, volume-sensitive Cl- currents were reduced at all membrane potentials (60 and 45% inhibition by 2 mM nedocromil and cromoglycate respectively). In contrast intracellular chromones were ineffective in BE cells. The relative refractoriness to chromones, in contrast with the high sensitivity shown by other Cl- channels, suggests that the epithelial volume-sensitive Cl- channel is not involved in asthma.

Antipyretic and anti-inflammatory efficacy of nimesulide vs paracetamol in the symptomatic treatment of acute respiratory infections in children.

To evaluate the clinical efficacy of nimesulide vs paracetamol in the treatment of acute inflammatory disorders of the airways, 40 paediatric patients (aged 3 to 12 years) with acute viral infections of the lower respiratory tract not requiring systemic antibiotic therapy in the first 3 days of observation were studied. Patients were randomly divided into 2 homogeneous groups receiving either oral nimesulide 1.5 mg/kg/day 3 times daily or paracetamol 120 to 288mg (5 to 12ml) 3 times daily for 3 to 7 days. Standard laboratory tests and chest x-rays were obtained at the beginning and end of treatment, and body temperature, blood arterial pressure and heart rate were recorded regularly. The anti-inflammatory effects of the 2 drugs (based on normalisation of erythrocyte sedimentation rate, C-reactive protein values, and white blood cell counts) were evaluated and the overall duration of the disease was assessed. The results showed that nimesulide was more effective than paracetamol in normalising body temperature (p < 0.05) and in reducing the inflammatory indices (p < 0.05), and that patients in the nimesulide group required a shorter treatment period than patients in the paracetamol group. No abnormal changes in arterial blood pressure or blood and urine analyses were seen in either group, and the reduction in heart rate was similar in both groups.

Human peripheral blood and pleural fluid eosinophils can be induced by immune complexes to release IgG immune complexes and aggregated IgE.

The ability of IgG and IgE immune complexes and of phorbol myristate acetate (PMA), a soluble membrane activator, to stimulate hydrogen peroxide (H2O2) release and to induce oxygen radical-mediated cytotoxic activity by human peripheral blood (PBL) eosinophils and by PBL neutrophils was evaluated in normal volunteers and patients with hypereosinophilic malignant pleural effusions due to lung cancer. PMA stimulated a significant respiratory burst. Similar results were obtained with IgG IC stimulation, although the levels of H2O2 were lower. Agg IgE induced H2O2 release only by PBL and PE eosinophils and not by neutrophils. PMA stimulation resulted in detectable cytotoxic activity. IgG IC generated both PBL and PE eosinophil and PBL neutrophil cytotoxicity. Agg IgE induced significant cellular cytotoxicity in both PBL and PE eosinophils. This study suggests that eosinophil oxidative metabolic burst and cytotoxic activity stimulated by IgG and IgE immune complexes could represent a possible mechanism of parenchymal injury in eosinophilic disorders.

BAL neutrophilia in asthmatic patients. A by-product of eosinophil recruitment?

Although neutrophil number may be increased in the airways of patients with asthma, its pathogenetic role in this disorder remains unclear. We evaluated BAL of 8 normal control subjects, 30 +/- 2 years of age, and 24 patients with mild asthma: 17 patients with allergic asthma, 24 +/- 1 years of age, and 7 patients with nonallergic asthma, 30 +/- 1 years of age. The BAL of asthmatic patients showed increased numbers of neutrophils (p < 0.01), eosinophils (p < 0.01), and ciliated epithelial cells (p < 0.05) and increased concentrations of myeloperoxidase (MPO) (p < 0.01) compared with control subjects. Positive correlations were observed between the number of BAL neutrophils and eosinophils (Rs = 0.780, p < 0.0001) and between BAL neutrophil numbers and BAL MPO levels (Rs = 0.40, p < 0.05). No correlations were found between the following: (1) BAL eosinophils or neutrophils and BAL epithelial cells (p > 0.05, each comparison); (2) BAL neutrophils or eosinophils and log Pd15 methacholine (MCh) (p > 0.05, each comparison); or (3) BAL epithelial cells or log Pd15 MCh and BAL MPO (p > 0.05, each comparison). Dividing the patient population into two groups, allergic asthmatics and nonallergic asthmatics, similar BAL neutrophil, eosinophil, and epithelial cell numbers and similar MPO levels were found (p > 0.05, each comparison). In addition, the correlations between BAL neutrophils and eosinophils showed similar significance in the two patient subgroups (p > 0.05, each comparison). These results suggest that, both in allergic and nonallergic asthma, airway recruitment and activation of neutrophils occur as does parallel eosinophil migration. However, airway neutrophils do not seem to contribute significantly to epithelial cell injury or to airway hyperresponsiveness in the steady state.

Survival after cytomegalovirus pneumonia in two children receiving autologous peripheral blood progenitor cell transplantation (PBPCT).

Cytomegalovirus (CMV) pneumonia is a very rare but often fatal complication of autologous bone marrow or peripheral blood progenitor cell transplantation. Diagnosis is usually made by means of CMV antigenemia which is strongly predictive of CMV disease. We describe two cases of PBPC transplantation who survived after CMV pneumonia which was diagnosed only by bronchoalveolar lavage in the absence of CMV-antigenemia.

Fiberoptic bronchoscopy and bronchoalveolar lavage for the evaluation of pulmonary infiltrates after BMT in children.

Thirty-one fiberoptic bronchoscopies and BAL performed within 4 days after the appearance of pulmonary infiltrates in 28 children who received BMT were reviewed. A causative agent was identified in 67% of patients with diffuse infiltrates (Cytomegalovirus in 8 cases, Pneumocystis carinii in 4) and in 31% of those with localized infiltrates (Aspergillus in 2, bacteria in 2). No relevant side effect was reported. The results obtained from cytological and microbiological testing provided relevant informations for the management of most cases, regardless to the identification of a specific pathogen. We conclude that BAL is a safe diagnostic procedure that should be considered early after the onset of pulmonary complications in BMT recipients.

Different expansions of T lymphocyte subpopulations in the lung and corticosteroid-induced changes in patients with active pulmonary sarcoidosis.

Pulmonary sarcoidosis is a disease characterized by increased numbers of T lymphocytes within the alveolar structures and the consequent spontaneous release of a variety of mediators relevant to the pathogenesis of this disorder. This phenomenon is associated with a different expansion of the T cell subpopulations present in the lung. Using monoclonal antibodies specific for T cell subsets with helper functions, we have evaluated the different T lymphocyte subpopulations present in patients with active and inactive pulmonary sarcoidosis. The small fraction of helper T cells recognized by the 5/9 monoclonal antibody appear to be preferentially expanded in the lung of patients with active disease. The functions of the 5/9+ lung T cells in pulmonary sarcoidosis were evaluated by considering the spontaneous release of monocyte chemotactic factor, the help in immunoglobulin production, and the spontaneous production of interleukin-2 by the 5/9+ lung T cells from patients with active disease. These T cell functions appeared to be restricted to the 5/9+ T cell subset. The sensitivity of the 5/9+ lung T cells to corticosteroid treatment in pulmonary sarcoidosis was studied by performing bronchoalveolar lavage in patients with active disease before and after oral prednisone therapy. Evaluation of lymphocyte subsets after 3 months of therapy showed a marked reduction of 5/9+ T cell percentages even though the overall proportion of lavage cells that were T lymphocytes was still elevated. Thus the 5/9 monoclonal antibody may be considered a good marker in gauging the activity of the alveolitis in pulmonary sarcoidosis because it recognizes the T cell subsets responsible for many activities relevant to the pathogenesis of this disorder. In addition, analysis of the proportions of 5/9+ lung T cells may result in a useful means to evaluate the early response to therapy.

Recurrent unilateral bacterial pneumonias and interstitial fibrosis associated with pulmonary vein atresia: successful treatment with endovascular stent implantation.

A variety of pulmonary vascular disorders, such as hemangiomatosis, telangectasia, and veno-occlusive disease, may be involved in the pathogenesis of interstitial lung diseases. We describe the case of a girl with recurrent bacterial pneumonia and progressive interstitial fibrosis affecting the right lung. Morphologic evaluation of the lung biopsy showed structural changes of the vessel walls suggesting pulmonary hypertension. The echocardiogram showed the presence of centripetal blood flow in the right pulmonary artery from the periphery of the lung to the heart. A selective right angiography demonstrated the presence of pulmonary venous obstruction at the veno-atrial junction, successfully treated by endovascular stent implantation during cardiac catheterization.

Mineral oil lipoid pneumonia in a child with anoxic encephalopathy: treatment by whole lung lavage.

We describe a case of exogenous lipoid pneumonia in a child with anoxic encephalopathy who was taking mineral oil for constipation. Computed tomography produced images suggesting this condition, and the diagnosis was confirmed by demonstrating the presence of lipid-laden alveolar macrophages in the bronchoalveolar lavage fluid. Despite discontinuing the offending agent, the pulmonary infiltrates did not improve; however, successful resolution was obtained by whole lung lavage.

Yellow nail syndrome and bilateral cystic lung disease.

In patients with yellow nail syndrome (YNS), highly characteristic nail changes are often associated with lymphedema and respiratory disorders due to pleural effusions or bronchiectasis. We describe a 4-year-old girl with the YNS who also had cystic lesions of the lung, affecting first the left lower lobe and, after surgical resection of the involved segments, also the right lower lobe. We discuss the etiology of the pulmonary cysts and hypothesize that abnormalities in pulmonary lymphatic flow, characteristic of YNS, may have decreased lung tissue compliance and determined the unusual progression of the cystic lesions in this patient.

Bronchoalveolar lavage and esophageal pH monitoring data in children with "difficult to treat" respiratory symptoms.

Gastroesophageal reflux (GER) may be associated with chronic or recurrent asthma-like symptoms secondary to bronchoconstrictor reflexes and/or inhalation of gastric content. The presence of lipid-laden alveolar macrophages has been proposed as an index to establish the degree of gastric aspiration. We evaluated 20 children with "difficult to treat" respiratory symptoms and a clinical history suggestive of GER. All children underwent 24-hr esophageal pH monitoring (pHm) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The amount of lipid per single macrophage was determined by a semiquantitative method, using fluorescence microscopy to detect Nile-Red-stained BAL cells and calculating a lipid-laden macrophage index (LLMI). Eleven children had positive pHm recordings, suggesting the presence of GER (pH-positive patients), and 9 had negative pHm records (pH-negative patients). The pH-positive patients had higher percentages of neutrophils and higher LLMI than the pH-negative children (P < 0.05). There were no correlations between the pHm records and either % BAL neutrophils or LLMI in pH-positive or pH-negative patients (P > 0.05; each correlation). In contrast, a single correlation was found between % BAL neuytrophils and LLMI, both in the pH-positive and in the pH-negative patients (r = 0.72, P = 0.02 and r = 0.71, P = 0.04, respectively). These data demonstrate that a significant proportion of pH-positive patients with respiratory symptoms have BAL abnormalities that suggest airway inflammation and gastric content aspiration. However, the intensity of GER as indicated by pH monitoring does not correspond with BAL data in all patients.

Outcome of laparoscopic Nissen-Rossetti fundoplication in children with gastroesophageal reflux disease and supraesophageal symptoms.

BACKGROUND: The role of surgery is debated for children with gastroesophageal reflux disease (GERD), particularly when they show atypical symptoms. This study was designed to evaluate the safety and outcome of laparoscopic Nissen-Rossetti fundoplication performed in a selected population of children with gastroesophageal reflux and atypical supraesophageal symptoms. METHODS: This prospective study included 595 patients younger than 14 years with GERD who reported recurrent respiratory symptoms and had no benefit from standard medical treatment. Surgery was performed for 48 patients with anatomic anomalies, life-threatening events, or respiratory complications after ineffective medical treatment. The subjective and objective outcomes were evaluated. RESULTS: No major intraoperative complications were experienced, and there was no recurrence of gastroesophageal reflux during a postoperative follow-up period of 12 months. The parents' final subjective evaluation of the outcomes 12 months after surgery was positive in 44 cases and negative in 4 cases. CONCLUSIONS: Children with difficult-to-treat chronic respiratory symptoms must be evaluated for GERD, even if the need for surgery is low (8%), because complete eradication of reflux is mandatory. Radical treatment of GERD allows the pulmonologist to perform correct respiratory treatment and to prevent the development chronic and life-threatening complications.