Correlations between exhaled nitric oxide levels and pH-metry data in asthmatics with gastro-oesophageal reflux.

BACKGROUND: In gastro-oesophageal reflux (GER), micro-aspirations of gastric fluid may damage the epithelial surface of the airways, an important source of endogenous nitric oxide (NO). OBJECTIVES: The aim of the study was to evaluate the possible influence of GER on fractional exhaled nitric oxide (FE(NO)) release. METHODS: FE(NO) levels were compared in two age-matched groups of allergic children: (1) 20 with mild asthma, responding to standard anti-asthma pharmacologic therapy (asthmatic children) and (2) 12 with mild 'asthma-like symptoms' and GER. RESULTS: No differences in pulmonary functions parameters (FEV(1), FVC and FEF(25-75%)) were found between the two groups of children (p > 0.1); FE(NO) levels were higher in asthmatic children compared with GER children (p = 0.0001). GER children underwent 24-hour oesophageal pH-metry, and possible correlations between pH-metry data, pulmonary functions and FE(NO) levels were evaluated. No correlations were found between pulmonary functions and pH-metry data (p > 0.05, each correlation). In contrast, correlations were observed between FE(NO) levels and pH-metry data, including (1) percentage of study time with pH < 4 (r = -0.80, p = 0.008), (2) number of episodes with pH < 4 (r = -0.76, p = 0.012), and (3) number of episodes >5 min with pH < 4 (r = -0.69, p = 0.02). CONCLUSIONS: Thus, FE(NO) levels are lower in allergic children with 'asthma-like symptoms' and GER as compared to asthmatic children. The correlations between FE(NO) levels and pH-metry data suggest that inhalation of acid gastric content may interfere with NO production in the airways.

Necessity for surgery in children with gastrooesophageal reflux and supraoesophageal symptoms.

BACKGROUND/PURPOSE: The majority of gastrooesophageal reflux (GER) manifestations in children are supraoesophageal, and "spitting/posseting" is "the tip of the iceberg" because most reflux episodes are not regurgitated. Aim of the present study was to prospectively evaluate the incidence of gastrooesophageal reflux and the incidence of antireflux surgery in patients with difficult-to-treat respiratory symptoms. PATIENTS AND METHODS: Five hundred and ninety-five children with difficult-to-treat respiratory symptoms were prospectively enrolled in a blind study looking for the correlation between clinical presentation (asthma or non-asthma), oesophageal pH monitoring, X-ray barium meal, broncho-alveolar lavage, necessity for surgery, and outcome. RESULTS: pH monitoring was anomalous in 47% of patients with asthma (group A) and in 43% of those who did not have asthma as main symptom (group B). Overall, 48 patients finally underwent anti-reflux surgery (8%) as anti-reflux medical treatment did not ensure stable benefits. No major surgical complications were experienced. Postoperatively, respiratory symptoms improved strongly (Visick 1) in 69% of cases, moderately (Visick 2) in 27%, while clinical worsening (Visick 4) was observed in 4%. CONCLUSIONS: The results of this study stress the importance of symptoms, clinical response to anti-reflux medical treatment and broncho-alveolar lavage compared to classical pH parameters in the decision-making process for patients with difficult-to-treat supraoesophageal symptoms. To date no single tool alone has proved to be diagnostic in these patients. Fundoplication is recommended only when a relationship between supraoesophageal symptoms and gastrooesophageal reflux is strongly suspected.

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.

e-NO peak versus e-NO plateau values in evaluating e-NO production in steroid-naive and in steroid-treated asthmatic children and in detecting response to inhaled steroid treatment.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P < 0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P < 0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

How can we best read exhaled nitric oxide flow curves in asthmatic children?

Orally exhaled nitric oxide (NO) levels are increased in children with asthma and thought to reflect the local inflammatory events in the airways. NO production in the lower respiratory airway is reflected in the plateau values of the NO curve, recorded while the patient is performing a slow vital capacity manoeuvre. In young patients, however, plateau values may be difficult to obtain, because the slow vital capacity manoeuvre is often terminated prematurely. In the present study, 60 steroid-naive atopic asthmatic children and 17 normal age-matched controls were asked to perform a slow vital capacity manoeuvre, during which fractional exhaled NO (FEno) levels were measured and evaluated as: a) FEno plateau levels of last part of exhalation (NO plateau); b) FEno peak values, c) area under the FEno curve (AUC). Thirteen out of the 60 steroidnaive patients were reevaluated after a short course of inhaled corticosteroid treatment. Independently of the type of data analysis, FEno values of asthmatics were significantly higher than those observed in normal controls (P < 0.001, each comparison). In addition, possibly because of upper airway NO contamination, FEno peak values were significantly higher than FEno plateau levels in asthmatic patients and in control subjects (P < 0.001, each comparison). Both in asthmatics and controls, highly positive correlations were observed between: a) FEno plateau and peak values (r > 0.7, P < 0.01, each correlation), b) FEno plateau and AUC values (r > 0.7, P < 0.01, each correlation) and c) FEno peak and AUC values (r > 0.9, P < 0.001, each correlation). In asthmatic patients, the three types of data analysis were equally sensitive in detecting the decrease in FEno levels induced by inhaled steroid therapy (P < 0.05, each comparison), with a good correlation between the three data analyses (r > 0.5, P < 0.05, each correlation). Thus, although quantitatively different, comparable data reflecting airway inflammation can be obtained evaluating FEno plateau, FEno peak, and area under the curve, on account of possible upper airway contamination in FEno peak, FEno plateau should be preferred to measure lower airway NO production.

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.

Nasal brushing: a clinically useful procedure in pediatric patients with rhinosinusitis?

Sinusitis is a common complication of non-allergic and allergic rhinitis, and can trigger lower respiratory diseases, such as bronchitis and asthma. Standard radiography is unable to give any data about the underlying pathological mechanisms (infectious or allergic) involved and infectious rhinosinusitis is very common in pediatric age, even in allergic patients. We investigated the possibility of obtaining more useful diagnostic information, performing nasal brushing (NB) on 117 children with recurrent respiratory symptoms. The following hypothesis were evaluated: (1) whether NB neutrophil/eosinophil percentages and/or NB culture could predict the radiological evidence of maxillary sinusitis; and (2) whether differences between nonallergic and allergic patients could be detected. In the total patient group and in the nonallergic group, the comparison of NB neutrophil percentages in patients with and without maxillary sinusitis showed a statistically significant difference (median 2 and 18%, respectively; P < 0.001). In the nonallergic group, a NB neutrophil rate > or = 5% was chosen as a cut-off between positive and negative NB diagnosis of rhinosinusitis and NB data were compared with radiological investigations. The results obtained showed that NB was fairly sensitive (91%) and predictive (84%). In allergic patients, neither neutrophil nor eosinophil percentages significantly correlated with the presence of sinusitis. Microbiological studies showed that, even if the presence of bacteria in NB resulted associated with sinusitis, a negative culture was not predictive of the absence of the disease. We therefore suggest that NB describes the present inflammatory status of the upper airways, hence, it is more suitable to describe the inflammation related to ongoing upper respiratory tract infections rather than chronic inflammation due to allergic rhinitis, characterized by relapsing episodes of acute inflammation. In conclusion, we propose to consider NB a reliable tool in the diagnosis of rhinosinusitis, particularly in nonallergic pediatric patients. Compared to standard radiological techniques, NB makes it possible to avoid radiation exposure and gives information about the pathological mechanisms involved in the single patient.

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma.

Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations. Twenty-two atopic children (aged 11.1+/-0.8 yrs) with mild-intermittent asthma, treated only with inhaled beta2-adrenoreceptor agonists on demand and 22 age-matched controls were studied. NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4+/-3.3 parts per billion (ppb) and 4.0+/-0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25-75% of vital capacity (FEF25-75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation). These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established.

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.

Severe endobronchial obstruction in a girl with relapsing polychondritis: treatment with Nd YAG laser and endobronchial silicon stent.

Relapsing polychondritis (RP) is an uncommon disorder of unknown aetiology characterized by inflammation and destruction of the cartilaginous structures of many organs, including the tracheobronchial tree. When untreated, there is a high mortality rate, usually from respiratory obstructive complications. An 8 year old white girl, with a previous diagnosis of RP, was referred to our department for evaluation of worsening dyspnoea. Bronchoscopy showed localized inflammatory and fibrotic alterations of the mucosa, leading to severe obstruction of the left mainstem bronchus at its origin. The condition was successfully treated by endoscopic neodymium yttrium aluminium garnet (Nd YAG) laser. Re-evaluation of the patient, 7 months later, demonstrated bronchial stenosis and malacia requiring mechanical dilatation and positioning of an endobronchial silicon stent, which was well-tolerated by the patient.

Common variable immunodeficiency presenting in a girl as lung infiltrates and mediastinal adenopathies leading to severe "superior vena caval" syndrome.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by decreased levels of circulating immunoglobulins (Ig) and increased susceptibility to infections. We describe the case of a girl, progressively developing CVID, whose first clinical manifestations were noninfectious diffuse pulmonary infiltrates and rapidly developing hilar and mediastinal lymphadenopathies causing a severe "superior vena caval syndrome". Histological evaluation of surgical samples showed follicular and paracortical hyperplasia of the lymph nodes and poorly organized, non-necrotizing, noninfectious, "reactive" granulomata in lymph nodes and pulmonary tissue. Daily treatment with azathioprine and prednisone induced resolution of the intrathoracic abnormalities but was associated with a progressive decrease of circulating IgG and IgA levels and natural killer (NK) lymphocytes that was not related to treatment. This case demonstrates that granulomatous inflammatory changes may be the first manifestations of common variable immunodeficiency, and that this disorder must be included in the differential diagnosis of lymphoid interstitial pneumonitis and of bilateral mediastinal lymph node enlargement leading to superior vena caval syndrome.

[Gastroesophageal reflux disease and respiratory disease]. / Malattia da reflusso gastro-esofageo e patologia respiratoria.

The patients treated for oesophageal atresia present a correlation between the clinical sintomatology after recanalization characterized by disfagia, dispnea, recurrent cough, chronic pneumopaties and oesophageal anomalies. Where morphological alterations accounting for the presence of gastro-oesophageal reflux (GOR) were not evident, possible functional alterations of the motility were considered. The incidence of GOR was considerably high and, expression of a congenital alteration of the lower oesophageal sphincter and of oesophageal peristalsis, becomes even more severe due to further stretching of the gastro-esophageal junction. The authors underline that the early demonstration of histological changes, even before recanalization, and the motility disorders of the oesophagus have to be well studied, while the LES is normalized, in order to prevent and treat the possible appearance of the well-known complications of GOR.

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.