The aim of the paper is to report the case of a boy affected by cystic fibrosis, with non-ABPA-related recurrent wheezing and frequent pulmonary exacerbation during childhood, who had been  inhaling 7% NaCl+0.1% hyaluronic acid (HA) as a maintenance therapy. We reviewed patient database and, analysing a 7-year follow-up, considered pulmonary exacerbation, antibiotic and steroid courses, pulmonary function (forced expiratory volume in one second; FEV1) and microbiological data. After starting 7% NaCl+0.1% HA treatment, we observed a dramatic decrease of oral antibiotic need (0.55 courses/month during the pretreatment period against 0.10 courses/month in the treatment period), associated with a good initial recovery and a stability of FEV1. In our opinion this case could suggest an extended indication for inhaled 7% NaCl+0.1% HA use in CF, not only in patients who did not tolerate hypertonic saline, but also in patients with coexistent asthma-like symptoms.

BACKGROUND:

The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear.

METHODS:

The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured.

RESULTS:

In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve.

CONCLUSION:

The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA.

The efficiency of various investigations and diagnostic criteria used in diagnosis of allergic bronchopulmonary aspergillosis (ABPA) remain unknown, primarily because of the lack of a gold standard. Latent class analysis (LCA) can provide estimates of sensitivity and specificity in absence of gold standard. Herein, we report the performance of various investigations and criteria employed in diagnosis of ABPA.Consecutive subjects with asthma underwent all the following investigations Aspergillus skin test, IgE levels (total and A.fumigatus specific), Aspergillus precipitins, eosinophil count, chest radiograph, and high-resolution computed tomography (HRCT) of the chest. We used LCA to estimate the performance of various diagnostic tests and criteria in identification of ABPA.There were 372 asthmatics with a mean age of 35.9 years. The prevalence of Aspergillus sensitization was 53.2%. The sensitivity and specificity of various tests were Aspergillus skin test positivity (94.7%, 79.7%); IgE levels>1000 IU/mL (97.1%, 37.7%); A.fumigatus specific IgE levels>0.35 kUA/L (100%, 69.3%); Aspergillus precipitins (42.7%, 97.1%); eosinophil count>1000 cells/µL (29.5%, 93.1%); chest radiographic opacities (36.1%, 92.5%); bronchiectasis (91.9%, 80.9%); and, high-attenuation mucus (39.7%, 100%). The most accurate criteria was the Patterson criteria using six components followed by the Agarwal criteria. However, there was substantial decline in accuracy of the Patterson criteria if components of the criteria were either increased or decreased from six.A.fumigatus specific IgE levels and high-attenuation mucus were found to be the most sensitive and specific test respectively in diagnosis of ABPA. The Patterson criteria remain the best diagnostic criteria however they have good veridicality only if six criteria are used.

Allergic bronchopulmonary aspergillosis (ABPA) is a common but frequently misdiagnosed clinical condition. It is usually diagnosed in patients with a long standing history of asthma. Patients with ABPA can have diverse radiological manifestations. Very rarely, lung masses have been reported. We hereby report a case of ABPA in whom a large symptomatic lung mass was the presenting manifestation leading to consideration of lung cancer as a differential diagnosis. The establishment of ABPA as the underlying diagnosis led to conservative medical treatment which was followed by complete resolution of the mass like opacity. The present case highlights that ABPA should be considered as a differential diagnosis whenever encountering a patient with lung mass and history of asthma.

Lung mycosis is rare. Diagnosis and treatment must be done the earliest possible.It is about a retrospective study on clinical records including patients hospitalized for lung infection.From 2008 to 2011, 16 patients (13 men and three women, average age 42 years) developed a pulmonary infection. Twelve of our patients had respiratory or extrarespiratory histories. None of our patients had a neutropenia. The diagnoses were lung aspergilloma in four cases, invasive lung aspergillosis in three cases, allergic bronchopulmonary aspergillosis in three cases, mucormycosis in three cases, trichosporonosis in a case, actinomycosis in one case and penicilliosis in one case. An antifungal treatment consisting in amphotericin B or itraconazole was given to four patients and six patients, respectively. Surgery was chosen for six patients. The evolution was good for 12 patients, one presented renal failure, and three patients died.

In patients with cystic fibrosis (CF), the isolation of filamentous fungi, in particular Aspergillus spp. in the respiratory secretions is a common occurrence. Most of these patients do not fulfil the clinical criteria for a diagnosis of allergic bronchopulmonary aspergillosis (ABPA). The clinical relevance of filamentous fungi and whether antifungal therapy should be started in patients with persistent respiratory exacerbations who do not respond to two or more courses of appropriate oral or intravenous antibiotics and in whom no other organisms are isolated from respiratory secretions is a dilemma for the CF clinician. In this article, we review the epidemiology and clinical significance of filamentous fungi in the non-ABPA CF lung, with an emphasis on Aspergillus spp. colonisation (AC), the clinical relevance of Aspergillus spp. positive respiratory cultures and the outcome following antifungal therapy in these patients.

OX40 ligand (OX40L) is a costimulatory molecule involved in Th2 allergic responses. It has been shown that vitamin D deficiency is associated with increased OX40L expression in peripheral CD11c(+) cells and controls Th2 responses to Aspergillus fumigatus in vitro in cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA). To investigate if vitamin D deficiency regulated OX40L and Th2 responses in vivo, we examined the effect of nutritional vitamin D deficiency on costimulatory molecules in CD11c(+) cells and A. fumigatus-induced Th2 responses. Vitamin D-deficient mice showed increased expression of OX40L on lung CD11c(+) cells, and OX40L was critical for enhanced Th2 responses to A. fumigatus in vivo. In in vitro assays, vitamin D treatment led to vitamin D receptor (VDR) binding in the promoter region of OX40L and significantly decreased the promoter activity of the OX40L promoter. In addition, vitamin D altered NF-κB p50 binding in the OX40L promoter that may be responsible for repression of OX40L expression. These data show that vitamin D can act directly on OX40L, which impacts Th2 responses and supports the therapeutic use of vitamin D in diseases regulated by OX40L.

Asthma is often triggered by allergic and nonallergic factors in atopic individuals and readily responds to anti-inflammatory and bronchodilator therapy. The differential diagnosis for poorly responsive disease includes severe persistent asthma with associated allergic rhinitis, cardiac disorders such as left ventricular failure or mitral stenosis, vocal cord dysfunction, gastroesophageal reflux disease, recurrent aspiration, chronic obstructive pulmonary disease, emphysema, alpha-1-antitrypsin deficiency, sarcoidosis, hypersensitivity pneumonitis, bronchiectasis, allergic bronchopulmonary aspergillosis, airway neoplasm, and Churg-Strauss vasculitis. A careful history and physical in conjunction with appropriate screening of laboratory information will usually direct the clinician to the correct diagnosis.

BACKGROUND:

Aspergillus often persists in the respiratory tract of patients with Cystic Fibrosis (CF) and may cause allergic broncho-pulmonary aspergillosis (ABPA). Chitinases are enzymes that digest the chitin polymer. Plants use chitinase as a defense mechanism against fungi. Chitotriosidase (CHIT1) is the major chitinase in human airways. Variation in the coding region with 24-bp duplication allele results in reduced CHIT1 activity. Recently, CHIT1 duplication heterozygocity was found in 6/6 patients with severe asthma and fungal sensitization (SAFS).

AIM:

Our aim was to evaluate the link between CHIT1 duplication in CF patients and the predisposition to Allergic broncho-pulmonary mycosis (ABPM) or persistent Aspergillus positive sputum (APS).

PATIENTS AND METHODS:

CHIT1 duplication was assessed in three CF groups. Group 1: patients who had neither ABPM nor APS in the past (control group). Group 2: patients with persistent APS (≥2/year), without ABPA. Group 3: patients with current or past ABPM.

RESULTS:

Forty patients with CF were included in the analysis, CHIT1 duplication heterozygocity was found in 3/6 (50%) of the patients in the ABPM group, 3/12 (25%) in the APS group, and 7/22 (31.8%) in the control group (P > 0.05). Eleven patients carried W1282X mutation, 90.9% were negative for CHIT1 duplication, five of them were homozygous for W1282X; none of them had CHIT1 duplication or ABPM.

CONCLUSIONS:

CHIT1 duplication is not found in all CF patients with ABPM in contrast to patients with SAFS. These results suggest that CHIT1 duplication cannot be the sole explanation for Aspergillus positive sputum in CF patients. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.

Detection of Aspergillus IgG antibodies is important in the diagnosis of chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Immunoprecipitation techniques to detect these antibodies appear to lack sensitivity and accurate quantitation compared with enzyme immunoassays (EIA). This study assessed the performance of two commercial EIAs compared with counterimmunoelectrophoresis (CIE). This was a prospective cohort study of 175 adult patients with chronic or allergic pulmonary aspergillosis. Aspergillus IgG antibodies were detected using CIE, Phadia ImmunoCap Aspergillus IgG and Bio-Rad Platelia Aspergillus IgG. Inter-assay reproducibility was determined for each method and 25 patients had two serum samples analysed within a 6-month interval. When compared with CIE, both ImmunoCap and Platelia Aspergillus IgG had good sensitivity (97 and 93%, respectively) for detection of Aspergillus IgG antibodies. The level of agreement between the two EIAs for positive results was good, but the concentration of antibodies was not correlated between the tests or with CIE titre. ImmunoCap IgG inter-assay coefficient of variation was 5%, whereas Platelia IgG was 33%. Median ImmunoCap IgG values for CPA and allergic aspergillosis were 95 and 32 mg/L, respectively, whereas Platelia IgG values were >80 and 6 AU/mL. The direction of CIE titre change over 6 months was mirrored by ImmunoCap IgG levels in 92% of patients, and by Platelia IgG in 72% of patients. Both ImmunoCap and Platelia Aspergillus IgG EIAs are sensitive measures of Aspergillus IgG antibodies compared with CIE. However, ImmunoCap appears to have better reproducibility and may be more suitable for monitoring patient disease.