Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia.

Few studies have evaluated the quality of life of patients with primary ciliary dyskinesia (PCD). We sought to determine the health impact of the disease as well as the unmet needs in a large group of patients. Questionnaires were either posted or e-mailed to known patients with PCD and published online. Questionnaires included the St George's Respiratory Questionnaire, the Medical Outcomes Study Short Form-36 and a questionnaire that we produced to obtain information on age of diagnosis, symptoms and likely PCD-specific problems of these patients. 78 subjects (96% of those invited) answered all the questionnaires. Patients were diagnosed at a mean age of 9.4 yrs. Progressive worsening of the disease was observed and adherence to physiotherapy was found to be poor, particularly in adolescents and adults. Patients with the highest treatment burden had a worse quality of life. Over time patients become progressively less interested in treating their disease and adherence to treatment modalities decreases. PCD is associated with a progressive and continuous impact on the physical and mental health of the patients. Earlier identification of the patients and better strategies aimed at improving compliance with care are urgently needed.

Long-term azithromycin in cystic fibrosis: another possible mechanism of action?

Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are not completely understood. Besides its antiinflammatory and antimicrobial activities, one possibility could be the overexpression induction of the multidrug resistance-associated protein (MRP), which could affect chloride transport, thus overcoming the ion transport defect of cystic fibrosis. Seven patients were evaluated before and after 4 weeks of azithromycin treatment (500 mg once daily). Ion transport was studied in vivo by measuring nasal potential difference (NPD). MRP mRNA expression was studied in nasal cells by an internal standard-based semiquantitative RT-PCR assay. NPD was consistent with cystic fibrosis before treatment. After azithromycin treatment, sodium transport was still impaired, whereas a significant increase in chloride conductance was observed (p = 0.03). A significant direct correlation was found between MRP mRNA expression levels and NPD chloride response after azithromycin treatment (p = 0.04, r = 0.78). In conclusion, azithromycin may induce MRP overexpression and restore chloride conductance in the airways of cystic fibrosis patients. These findings suggest a new potential role of azithromycin in the treatment of cystic fibrosis pulmonary disease, i.e. the possibility to upregulate proteins whose function may, at least in part, compensate for the basic defect of cystic fibrosis.

Early bronchopulmonary involvement in Crohn disease: a case report.

BACKGROUND: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. CASE PRESENTATION: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. CONCLUSIONS: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD.

Evidence of mild respiratory disease in men with congenital absence of the vas deferens.

Cystic fibrosis (CF) is a severe disorder, whose main characteristics are, in addition to congenital absence of the vas deferens (CAVD), progressive lung disease, pancreatic insufficiency and elevated sweat chloride levels; CAVD without any other manifest clinical evidence is commonly suggested to be a form of CF with primarily genital expression. We undertook this study to test the hypothesis that men with a CAVD phenotype could be more CF-like than it is usually assumed. Each subject from a population of 42 patients suffering from CAVD was screened for a panel of 16 mutations plus the intron 8 5-thymidine allele of the CF gene (5T), and underwent a thorough clinical evaluation which included a detailed anamnesis, anthropometric data, chest and paranasal sinuses X-rays, pulmonary function tests, sputum cultures, stool chymotrypsin determination, sweat test and, in a limited number of patients, Nasal Potential Difference (NPD) measurement. The genotype analysis detected one compound heterozygote, 23 heterozygotes and 15 individuals carrying the 5T allele; sweat chloride was positive in six, borderline in 11 and negative in 25 subjects; NPD was abnormal in 2/12 patients. Medical history and clinical examination were consistent with respiratory disease in 20 cases; there was radiological evidence of pulmonary hyperinflation in 37/39 and of sinus disease in 20/42 patients; Staphylococcus aureus was cultivated in the sputum of 9/36, Haemophilus influentiae in 3/36 subjects and three patients showed functional evidence of airway obstruction. These findings were equally distributed among sweat positive, borderline and negative patients. These results raise questions about the supposed benignancy of the CAVD condition. A close follow-up of men with CAVD could ascertain potential complications.

Nasal potential difference in congenital bilateral absence of the vas deferens.

Congenital bilateral absence of the vas deferens (CBAVD) is supposed to be due to defective activity of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) in the genital tract. With the aim of studying CFTR activity in vivo we measured nasal potential difference (NPD) in a group of CBAVD subjects, who were then compared with normal control subjects and CF patients. Sodium transport, measured under basal conditions and after amiloride superinfusion, was normal in almost all CBAVD patients, who had NPD values similar to those of normal control subjects. Chloride transport was studied by measuring NPD during perfusion with a chloride-free solution and isoproterenol. Under these circumstances CBAVD patients as a whole showed normal chloride secretion. However, three subjects with CBAVD had abnormal NPD values. They had either elevated sweat chloride concentrations together with symptoms of mild CF, or compound heterozygosity (DeltaF508/R117H). In conclusion the group of CBAVD patients as a whole presented normal bioelectric properties of nasal epithelium, suggesting normal CFTR activity. In a small subgroup NPD was abnormal, suggesting a diagnosis of CF, later confirmed by elevated sweat chloride concentrations or positive DNA testing. We suggest that CBAVD patients with altered NPD should undergo further clinical follow-up in order to detect possible late complications of CF.

Nasal potential difference in cystic fibrosis patients presenting borderline sweat test.

The diagnosis of cystic fibrosis (CF) can be difficult if the sweat test and routine deoxyribonucleic acid (DNA) analysis are inconclusive. Under these circumstances, measurement of nasal potential difference (NPD) was proposed as a complementary diagnostic tool, as demonstrated in subjects bearing the G551S or 3849+10KbC-->T mutations. The purpose of the present study was to verify the diagnostic value of this technique in CF patients with a borderline sweat test. NPD was measured in 18 patients with a borderline sweat test, in whom CF diagnosis was based on the presence of one CF gene mutation in each chromosome (CF borderline). These patients were compared both to non-CF controls and CF patients with an abnormal sweat test (CF controls). Basal NPD values of CF borderline patients (mean value -39+/-6 mV, range -29 to -52 mV; n=18) were in the pathological range of CF controls (-39+/-8 mV, range -28 to -57 mV; n=37), and both were statistically different from values obtained in non-CF controls (-15+/-4 mV, range -6 to -23 mV; n=24; p<0.0001). Mutation analysis confirmed a high frequency of the 3849+10KbC-->T mutation in this group of CF borderline patients (positive in 14 out of 18 subjects), whereas other mutations, such as AF508, Q552X, N1303K and R1162X, were also found to be associated with this atypical CF phenotype. These results confirm the presence of pathological values of basal NPD in CF patients with borderline sweat test, and also extend this finding to subjects bearing genotypes other than the G551S and 3849+10KbC-->T mutations. The present findings, therefore, confirm the usefulness of measurement of basal nasal potential difference in all those patients in whom diagnosis of cystic fibrosis can be suspected but the sweat test remains inconclusive.

Effect of different inspiratory maneuvers on FEV1 in patients with cystic fibrosis.

The time course of inspiration has been shown to have a significant influence on the subsequent maximal expiratory flows and timed forced expiratory volumes in healthy adults and those with COPD. The purpose of this study was to evaluate the effect of two different inspiratory maneuvers on the spirogram in 15 patients with cystic fibrosis, aged 13 to 35 years, who had mild to moderate airway obstruction. Patients performed a forced expiratory maneuver either after a rapid inspiration without an end-inspiratory pause or after a slow inspiration with a 4-s end-inspiratory pause. Flow-time and volume-time curves were measured by a pneumotachograph. The mean values of FVC, FEV1, and peak expiratory flow were significantly larger by 11%, 13%, and 26%, respectively, after the rapid inspiration without an end-inspiratory pause compared to the slow inspiration with the end-inspiratory pause. This discrepancy probably reflects differences in effective elastic recoil pressure between the two maneuvers. Although the nature of this phenomenon is not fully understood, our results show that for spirometry in patients with cystic fibrosis, the preceding inspiratory maneuver influences the results. An important corollary is that this inspiratory maneuver should be standardized.

Determinants of maximal transdiaphragmatic pressure in adults with cystic fibrosis.

To investigate whether diaphragmatic strength could be reduced in cystic fibrosis (CF), and to examine possible mechanisms leading to diaphragmatic weakness, we measured transdiaphragmatic pressure (Pdi), together with lung mechanics, including dynamic "intrinsic" positive end-expiratory pressure (PEEPi,dyn), ventilation, lung volumes, and nutritional status in 15 adult patients with CF in stable clinical condition. Diaphragmatic strength was assessed as the maximum Pdi (Pdimax). Nutritional assessment included the calculation of weight as a percentage of ideal weight for height (Wt/Ht). On average, our 15 CF patients had airway obstruction (FEV1 = 59 +/- 28% predicted) and a small PEEPi,dyn (1 +/- 0.7 cm H2O). Functional residual capacity average 52 +/- 9% of the predicted total lung capacity. The Wt/Ht was normal on average (95%), but with a large range from malnutrition to a good nutritional status (76 to 109%). We found that Pdimax decreased with increasing FRC/TLC percent predicted (r = 0.55, p < 0.05), but more significantly with decreasing Wt/Ht (r = 0.76, p < 0.001). The multiple linear regression analysis for these factors was significant (R2 = 0.70, p < 0.05); however, the partial regression coefficient was significant only for Wt/Ht (p < 0.01). These results suggest that in CF patients, diaphragmatic strength decreases with the progression of the disease, increasing lung volume and worsening nutritional status, and that malnutrition is the strongest determinant of diaphragmatic weakness.

Hemoglobin desaturation during sleep and daytime in patients with cystic fibrosis and severe airway obstruction.

Transcutaneous hemoglobin saturation by pulse oximetry was evaluated during sleep and for 2-3 h during the day in 31 patients with cystic fibrosis (median age 15.2 years; range 7.6-33.6 years) and severe airway obstruction. Pulse oximetry readings were analyzed as a cumulative percentage of time in which oxygen saturation was < 90% during both sleep and daytime. Each patient was also examined using clinical and radiological scores, spirometry and arterial blood-gas analysis. The agreement between arterial and transcutaneous saturation was evaluated in 29 patients. The difference between transcutaneous and arterial saturation was 2.4 +/- 2.0% and it increased as arterial saturation decreased. Clinical and radiological scores and spirometry parameters showed a poor correlation with both overnight and daytime desaturation. An arterial saturation < 94% may indicate a risk of consistent desaturation. This occurred for more than 50% of the time in 11 of 20 patients during sleep and in 5 of 20 patients during daytime hours.

[Ciprofloxacin: an alternative oral treatment in respiratory Pseudomonas infection in cystic fibrosis]. / Ciprofloxacin: un'alternativa di trattamento orale nell'infezione respiratoria da Pseudomonas in fibrosi cistica.

20 CF patients, aged from 16.5 to 31.7 years, with chronic pulmonary infection due to Pseudomonas, were included in an open trial to study the efficacy of ciprofloxacin on respiratory exacerbation. Ciprofloxacin was given orally at the dose of 1500 mg/die for ten days. 16 patients concluded the entire treatment with clear clinical improvement, based on a score including 11 parameters. There has also been a significant improvement in the pulmonary function tests, and a tendency of Rx score to decrease. 4 patients interrupted the treatment on the fifth day because of clinical inefficacy. There was no increase of Pseudomonas resistance to ciprofloxacin at the end of the treatment; 30 days after no strain of pseudomonas was found resistant. We observed side-effects in 5 patients, but in no case it was necessary to discontinue the treatment. Ciprofloxacin may be considered as a good alternative to the more established antibiotic strategy in the treatment of Pseudomonas lung exacerbations in CF.

Transcutaneous blood gas analysis during sleep and exercise in cystic fibrosis.

Forty patients with cystic fibrosis (CF) (mean age, 13 +/- 2.5 years) were studied with transcutaneous (tc) blood gas monitoring (TCM) during sleep and exercise. By comparing arterial blood samples and TCM in 24 of them (27 samples), a mean bias of tcO2 -15.91 mmHg with a precision of 8.4 mmHg was found. The mean bias of tcCo2 was 7.21 mmHg with a precision of 3.9 mmHg. A standardized submaximal exercise test (1.7 W/kg) was performed in all 40 CF patients and in 14 healthy control subjects (mean age, 13 +/- 0.5 years). The typical tc trend during exercise for CF and healthy subjects was a slight increase of tcO2 levels and tcCO2 stability. A minor decrease of tcO2 values occurred in four CF patients (no greater than 7 mmHg). In 28 patients (mean age, 13 +/- 3 years), tcO2 and tcCO2 were recorded during sleep. In 13 of them, apparent hypoxemic episodes were noted, without relation to the degree of airway obstruction. There were simultaneous episodes of hypercapnia in ten patients. Some difficulties were encountered in analyzing long-term recordings. TcO2 drifts upward and tcCO2 decreases during the recordings over several hours. The change in electrode position after 4 h of sleep modified tcO2 and tcCO2 values. Such difficulties limit the usefulness of long-term but not short-term recordings.