Abstract: Asthma is a common disorder that in 2009 afflicted 8.2% of adults and children, 24.6 million persons, in the United States. In patients with moderate and severe persistent asthma, there is significantly increased morbidity, use of health care support, and health care costs. Epidemiologic studies in the United States and Europe have associated mold sensitivity, particularly to Alternaria alternata and Cladosporium herbarum, with the development, persistence, and severity of asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. Allergic bronchopulmonary aspergillosis (ABPA) is caused by A fumigatus and is characterized by exacerbations of asthma, recurrent transient chest radiographic infiltrates, coughing up thick mucus plugs, peripheral and pulmonary eosinophilia, and increased total serum IgE and fungus-specific IgE levels, especially during exacerbation. The airways appear to be chronically or intermittently colonized by A fumigatus in patients with ABPA. ABPA is the most common form of allergic bronchopulmonary mycosis (ABPM); other fungi, including Candida, Penicillium, and Curvularia species, are implicated. The characteristics of ABPM include severe asthma, eosinophilia, markedly increased total IgE and specific IgE levels, bronchiectasis, and mold colonization of the airways. The term severe asthma associated with fungal sensitization (SAFS) has been coined to illustrate the high rate of fungal sensitivity in patients with persistent severe asthma and improvement with antifungal treatment. The immunopathology of ABPA, ABPM, and SAFS is incompletely understood. Genetic risks identified in patients with ABPA include HLA association and certain T(H)2-prominent and cystic fibrosis variants, but these have not been studied in patients with ABPM and SAFS. Oral corticosteroid and antifungal therapies appear to be partially successful in patients with ABPA. However, the role of antifungal and immunomodulating therapies in patients with ABPA, ABPM, and SAFS requires additional larger studies.

Abstract: Rationale: The vicious cycle hypothesis of bronchiectasis argues that bacterial colonization leads to airway inflammation and progressive lung damage. The logical extension of this hypothesis is that acute or chronic antibiotic therapy should improve airway inflammation and clinical outcome. There are little data to support this hypothesis in patients with non–cystic fibrosis (CF) bronchiectasis.Objectives: To determine whether acute or chronic antibiotic therapy improves airway inflammation and clinical outcome in non-CF bronchiectasis.Methods: The relationship between bacterial load and airway and systemic inflammation was investigated in 385 stable patients, 15 stable patients treated with intravenous antibiotics, and 34 patients with an exacerbation of bronchiectasis treated with intravenous antibiotics. Long-term antibiotic therapy was investigated using samples from a 12-month controlled trial of nebulized gentamicin.Measurements and Main Results: In stable patients, there was a direct relationship ...

Abstract: Pleuroparenchymal fibroelastosis (PPFE) is a rare condition characterised by predominantly upper lobe pleural and subjacent parenchymal fibrosis, the latter being intra-alveolar with accompanying elastosis of the alveolar walls. The aim of this study was to review cases fulfilling published imaging and histological criteria, and identify any common clinical features that may suggest an underlying aetiology for a condition that has previously been regarded as idiopathic. Of 12 patients (seven females, median age 57 yrs), the presenting symptoms were shortness of breath (11 out of 12 patients) and dry cough (six out of 12 patients). Seven patients reported recurrent infections during the course of their disease. Five demonstrated nonspecific autoantibody positivity. Two patients had a family history of interstitial lung disease (ILD). High-resolution computed tomography features of lung disease remote from the pleuroparenchymal changes were present in six out of 12 patients (coexistent fibrosis, n=5; bronchiectasis, n=1). Of seven patients with tissue sampled from the lower lobes, four patients showed less intense PPFE changes (one with additional features of hypersensitivity pneumonitis) and three showed usual interstitial pneumonia. PPFE is a distinct clinicopathological entity, with clinical data suggesting a link to recurrent pulmonary infection. Genetic and autoimmune mechanisms may also contribute to the development of these changes. PPFE may also present with more diffuse involvement than previously reported, and coexist with different patterns of ILD.

Abstract: Objective To evaluate the presence of pulmonary abnormalities in rheumatoid arthritis (RA)–related autoantibody–positive subjects without inflammatory arthritis. Methods Forty-two subjects who did not have inflammatory arthritis but were positive for anti–cyclic citrullinated peptide antibodies and/or ≥2 rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 autoantibody-negative controls, and 12 patients with established seropositive early RA (<1-year duration) underwent spirometry and high-resolution computed tomography (HRCT) lung imaging. Results The median age of autoantibody-positive subjects was 54 years, 52% were female, and 38% were ever-smokers; these characteristics were not significantly different from those of autoantibody-negative control subjects. No autoantibody-positive subject had inflammatory arthritis based on joint examination. HRCT revealed that 76% of autoantibody-positive subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities, and air trapping, compared with 33% of autoantibody-negative controls (P = 0.005). The prevalence and type of lung abnormalities among autoantibody-positive subjects were similar to those among patients with early RA. In 2 autoantibody-positive subjects with airways disease, inflammatory arthritis classifiable as articular RA developed ∼13 months after the lung evaluation. Conclusion Airways abnormalities that are consistent with inflammation are common in autoantibody-positive subjects without inflammatory arthritis and are similar to airways abnormalities seen in patients with early RA. These findings suggest that the lung may be an early site of autoimmune-related injury and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA.

Abstract: Background: Infection and inflammation are important in the pathogenesis of bronchiectasis. However, there are few published data describing the lower airway microbiology and cellularity in children. Methods: Children with non-cystic fibrosis (CF) bronchiectasis who underwent bronchoalveolar lavage (BAL) within 4 weeks of diagnosis were identified by a retrospective patient-record review. The effects of infection (>= 10(5) colony-forming units of respiratory bacteria/ml; or detectable Pseudomonas aeruginosa; mycobacteria, fungi, mycoplasma, or respiratory viruses) on airway cellularity and the impact of age, gender, indigenous status, immune function, radiographic involvement and antibiotic usage on infection risk were evaluated. Results: Of 113 children [ median age 63 months (IQR 32-95)] with newly diagnosed bronchiectasis, 77 (68%) had positive BAL cultures for respiratory bacterial pathogens. Haemophilus influenzae was most commonly detected, being present in 53 (47%) BAL specimens. P. aeruginosa was found in just 7 (6%) children, five of whom had an underlying disorder, while mycobacterial and fungal species were not detected. Respiratory viruses were identified in 14 (12%) children and Mycoplasma pneumoniae in two others. Overall, 56 (49.5%) children fulfilled our definition of a lower airway infection and of these, 35 (63%) had more than one pathogen present. Compared to children without infection, children with infection had higher total cell counts (610 vs. 280 X 10(6)/L), neutrophil counts (351 vs. 70 X 10(6)/L), and neutrophil percentages (69% vs. 34%). Age at diagnosis was most strongly associated with infection. Conclusions: BAL microbiology of children with newly diagnosed bronchiectasis is dominated by H. influenzae. In the absence of CF, isolation of P. aeruginosa may suggest a serious comorbidity in this group. Airway neutrophilia is common, especially with higher bacterial loads. Pediatr Pulmonol. 2012; 47:300-307. (C) Wiley Periodicals, Inc.

Abstract: There is a relative lack of information about the death rate and morbidity of non-cystic fibrosis bronchiectasis and most studies are limited due to referral bias We wanted to assess death rate and morbidity in those patients at our hospital Adult patients seen at our department between June 2006 and November 2009 were recruited if the key string "bronchiect-" was mentioned in electronic clinical records and if chest CT imaging was available Clinical records of all patients with confirmed radiologic diagnosis of bronchiectasis were reviewed and clinical characteristics were analyzed 539 patients with a radiographic diagnosis of non-cystic fibrosis bronchiectasis were identified in a retrospective cross-sectional analysis giving a prevalence of 26% in our hospital population A wide range of etiologies was found with idiopathic bronchiectasis in 26% In the 41 months interval, 57 patients (106%) died We found a median exacerbation rate of 194 per year Bacterial colonization status was associated with more deaths, exacerbation rate, symptoms and reduced pulmonary function Pulmonary hypertension was found in 48% of our patients We evaluated a large non-cystic fibrosis bronchiectasis population, and provided new epidemiological data on associations between clinical characteristics and deaths and morbidity in these patients

Abstract: Aspergillus bronchitis is poorly understood and described We extracted clinical data from more than 400 referred patients with persistent chest symptoms who did not fulfill criteria for allergic, chronic, or invasive aspergillosis Symptomatic patients with a positive culture or real-time PCR for Aspergillus spp were reviewed Seventeen patients fulfilled the selected criteria Fourteen were women, with a mean age of 57 years (range 39-76) Sixteen of the patients had productive cough, eight had voluminous tenacious sputum, and seven had recurrent chest infections Eight patients had Medical Research Council dyspnea scores of 4-5; 12 had bronchiectasis; and 13 patients grew A fumigatus, 3 A niger, and 1 A terreus Twelve of the 17 patients (71%) had elevated Aspergillus IgG (47-137 mg/L, mean 892) and 5 (29%) had elevated Aspergillus precipitins Six of 12 (50%) had a major response to antifungal therapy and five of 12 (42%) patients relapsed, requiring long-term therapy Aspergillus bronchitis is a discrete clinical entity in patients with structural lung disease but who are not significantly immunocompromised It is distinct from asymptomatic fungal colonization and other forms of aspergillosis, and may respond to antifungal therapy

Abstract: Rationale Exacerbations in non-cystic fibrosis (CF) bronchiectasis are associated with worsening lung functions and quality of life. A standardized definition of exacerbation could improve clinical care and research. Methods: A cohort of 69 children with non-CF bronchiectasis was prospectively followed for 900 child-months. The changes in clinical, systemic, and lung function parameters from 81 exacerbations were statistically evaluated using conditional logistic regression, receiver operating characteristic, sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) to formulate a definition of a pulmonary exacerbation. Formation of major and minor criteria was statistically based and models were developed. Measurements and Main Results: Wet cough and cough severity (score >= 2) over 72-hr were the best predictors of an exacerbation with area under the curve (AUC) of 0.85 (95% CI 0.79-0.92) and 0.84 (95% CI 0.77-0.91), respectively. Sputum color, chest pain, dyspnea, hemoptysis, and chest signs were significant though minor criteria. Inclusion of serum C-reactive protein, amyloid-A, and IL6 to the definition improved its specificity and PPV. Our final combined model consisted of one major with one investigatory criterion (PPV 91%, NPV 72%); two major criteria (PPV 79%, NPV 91%); or one major and two minor criteria (PPV 79%, NPV 94%). Conclusions: Pulmonary exacerbation in children with non-CF bronchiectasis can be validly predicted using a standardized assessment of clinical features, with additional systemic markers improving predictive values. This definition potentially facilitates earlier detection (leading to appropriate management) of exacerbations. Pediatr Pulmonol. 2012; 47: 68-75. (C) 2011 Wiley Periodicals, Inc.

Abstract: However, in diseases charac-terized by chronic neutrophilic inflammation such as ciga-rette-smoke-induced chronic obstructive pulmonary disease(COPD) and cystic fibrosis (CF) lung disease, excessive NEactivity has been implicated in proteolytic damage of theairways and lung parenchyma causing bronchiectasis andemphysema, ultimately leading to respiratory failure anddeath.

Abstract: Background and objective: Chest MRI is increasingly used to assess pulmonary diseases, but its utility compared with high-resolution computed tomography (HRCT) has never been evaluated in children using specific performance outcomes. The aim of this study was to assess the accuracy and reliability of MRI compared with HRCT in children with non-cystic fibrosis (CF) chronic lung disease. Methods: Fifty subjects aged 5.9–20 years, with primary ciliary dyskinesia (n = 17), primary immunodeficiency (n = 17) or recurrent pneumonia (n = 16), underwent chest HRCT and MRI. The prevalence of lung abnormalities on HRCT was evaluated, and sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI versus HRCT were calculated. MRI and HRCT scans were also assessed using a modified Helbich score. Results: Bronchiectasis, mucous plugging, peribronchial wall thickening, consolidation, bullae, abscesses and emphysema were detected by HRCT in 72, 68, 66, 60, 10, 8 and 8% of subjects, respectively. Sensitivity, specificity, accuracy and positive and negative likelihood ratios for MRI were good or excellent for most of the changes that were assessed. Median total Helbich scores for HRCT and MRI were 10 (range 0–20) and 10 (range 0–18), respectively. There was good-to-excellent agreement between the two techniques for all scores (r ≥ 0.8). A Bland–Altman plot confirmed this agreement between total scores (bias value: 0.2 ± 1.18; 95% limits of agreement of mean difference: −2.12–2.52). Conclusions: Chest MRI was equivalent to HRCT to determine the extent of lung disease in children with non-CF lung disease. The findings support the use of chest MRI as an alternative to HRCT in diagnostic pathways for paediatric chronic lung disorders.

Abstract: Introduction Bronchiectasis is a well-known sequela of chronic pulmonary aspiration (CPA) that can result in significant respiratory morbidity and death. However, its true prevalence is unknown because diagnosis requires high resolution computed tomography which is not routinely utilized in this population. This study describes the prevalence, time course for development, and risk factors for bronchiectasis in children with CPA. Materials and Methods Using a cross-sectional design, medical records were reviewed for all patients with swallow study or airway endoscopy-confirmed aspiration in our airway center over a 21 month period. All patients underwent rigid and flexible bronchoscopy, and high resolution chest computed tomography. Prevalence, distribution, and risk factors for bronchiectasis were identified. Results One hundred subjects age 6 months to 19 years were identified. Overall, 66% had bronchiectasis, including 51% of those less than 2 years old. The youngest was 8 months old. Severe neurological impairment (OR 9.45, P < 0.004) and history of gastroesophageal reflux (OR 3.36, P = 0.036) were identified as risk factors. Clinical history, exam, and other co-morbidities did not predict bronchiectasis. Sixteen subjects with bronchiectasis had repeat chest computed tomography with 44% demonstrating improvement or resolution. Discussion Bronchiectasis is highly prevalent in children with CPA and its presence in young children demonstrates that it can develop rapidly. Early identification of bronchiectasis, along with interventions aimed at preventing further airway damage, may minimize morbidity and mortality in patients with CPA. Pediatr Pulmonol. 2012; 47:447–452. © 2011 Wiley Periodicals, Inc.

Abstract: Background and Purpose. Although the application of airway clearance techniques is considered an important component in the treatment of several obstructive pulmonary diseases, there is no scientific evidence supporting the use of Flutter Valve™ in the management of patients with bronchiectasis. Moreover, the consequences of respiratory physiotherapy techniques on respiratory mechanics have not been fully studied. Therefore, we investigated the acute, short-term effects of Flutter Valve™ on respiratory mechanics and sputum production in bronchiectatic patients. Methods. Eight patients were evaluated in a randomized, blinded, cross-over trial. Impedance at 5 Hz (R5), resistance as a function of oscillation frequency (dR/dF), reactance at 5 Hz (X5), resonant frequency (f0) and integral of reactance between 5 Hz and resonant frequency (AX) were recorded. Results. Flutter Valve™ cleared 8.4 mL more secretions than the Sham Flutter intervention (95% confidence interval [95% CI], 3.4–13.4). There was a higher percentage decrease in R5 (−11.2%; 95% CI, −4.4 to −18.2), dR/dF (−20.8%; 95% CI, −32.4 to −9) and AX (−7.8%; 95% CI, −11.9 to −3.7) under Flutter Valve™. X5 and f0 variation did not differ between interventions. Conclusions. Flutter Valve™ increases sputum removal during treatment and diminishes total and peripheral airway resistance in hypersecretive patients with bronchiectasis. Impulse oscillometry is a user-friendly tool to evaluate the effects of airway clearance techniques on respiratory mechanics. Copyright © 2010 John Wiley & Sons, Ltd.

Abstract: Mycoplasma pneumoniae is an atypical bacterial pathogen without a cell wall that affects both the upper and lower respiratory tracts of children and adults. It is implicated in airway diseases including pneumonia, exacerbation of wheezing, tracheobronchitis, and pharyngitis, as well as extrapulmonary manifestations such as neurological, hematologic, gastrointestinal, and dermatological pathologies [1, 2]. Among M. pneumoniae–infected patients, it is estimated that 3%–10% develop clinical pneumonia and that <5% of cases of pneumonia are severe enough to require hospitalization. M. pneumoniae–mediated fulminant pneumonia is considered to be rare, regardless of the high prevalence of the infection in the general population [1, 2]. Although M. pneumoniae has been recognized as a significant clinical pathogen for decades, its virulence determinants have only been partially deciphered. Recently, we identified a unique M. pneumoniae adenosine diphosphate-ribosylating and vacuolating cytotoxin (designated community-acquired respiratory distress syndrome [CARDS] toxin) [3]. The severity of pulmonary disease caused by M. pneumoniae appears to be dependent on biological properties of individual mycoplasma strains and CARDS toxin concentration [4]. Interestingly, CARDS toxin transcription and translation are substantially up-regulated during infection, in contrast to in vitro growth [5]. Furthermore, CARDS toxin shares similarities to the toxin of Bordetella pertussis [3, 6]. The pulmonary presentations of M. pneumoniae pneumonia have included cellular bronchiolitis [7], bronchiolitis obliterans with organizing pneumonia (BOOP) or without organizing pneumonia [7–9], bronchiectasis, pleural effusion, adult respiratory distress syndrome [10], pulmonary embolism [11], chronic interstitial fibrosis [12], and lung abscess [13]. The current literature stresses the benign and often subclinical nature of many of these infections; hence, the term “walking pneumonia” is sometimes used to describe M. pneumoniae pneumonia. However, cases of fulminant pneumonia due to M. pneumoniae have been encountered with resultant respiratory failure or death [8]. In this study, we describe a range of clinical manifestations associated with M. pneumoniae infection in a previously healthy family. To our knowledge, for the first time, M. pneumoniae–mediated disease progression is described in terms of mycoplasma load, CARDS toxin detection, and individual subject immunological and clinical responsiveness to infection.

Abstract: AIM: To investigate the chest radiographic and high resolution computed tomography (HRCT) chest manifestations in glucocorticoid-naive allergic bronchopulmonary aspergillosis (ABPA) patients. METHODS: This is a prospective observational study and includes 60 consecutive glucocorticoid-naive patients with ABPA who underwent chest radiography and HRCT of the chest (1.25 mm every 10 mm) in the routine diagnostic workup for ABPA. RESULTS: Chest radiographs were normal in 50% of cases. Of the remainder, most patients demonstrated permanent findings in the form of parallel line and ring shadows suggesting bronchiectasis. Consolidation was detected in 17 cases but in the majority, the corresponding HRCT chest scan showed mucus-filled bronchiectatic cavities. Chest HRCT was normal in 22 patients, while central bronchiectasis (CB) was demonstrated in the remaining 38 patients. Bronchiectasis extended to the periphery in 33%-43% depending on the criteria used for defining CB. The other findings observed on HRCT were mucoid impaction, centrilobular nodules and high-attenuation mucus in decreasing order of frequency. CONCLUSION: Patients with ABPA can present with normal HRCT chest scans. Central bronchiectasis cannot be considered a characteristic feature of ABPA as peripheral bronchiectasis is commonly observed. Consolidation is an uncommon finding in ABPA.

Abstract: Bronchiectasis is a chronic inflammatory lung disease, which has similarities to chronic obstructive pulmonary disease (COPD). Comorbidities of COPD include increased risk of cardiovascular (CV) disease, loss of bone mineral density (BMD) and loss of skeletal muscle mass and function, all linked to systemic inflammation. The potential for such comorbidities has not been explored in bronchiectasis. We hypothesised that patients with bronchiectasis would have similar increased comorbidities. A total of 20 patients with noncystic fibrosis bronchiectasis were compared to 20 controls similar in age, gender and smoking exposure. Assessments included aortic pulse wave velocity (PWV; (a measure of arterial stiffness and an independent predictor of CV risk), blood pressure (BP) as well as levels of interleukin-6 (IL-6), albumin, fasting glucose and lipids. Body composition (fat free mass index (FFMI)), BMD, the 6-min walk distance (6MWD) and self-reported physical activity were also determined. Patients with bronchiectasis had increased aortic PWV, 10.5 (3.0) m/second, when compared with controls, 8.8 (1.6) m/second (p < 0.05), despite similar central and peripheral BP and lipid profile. Patients also had increased IL-6 and reduced albumin and glucose. Although mean body mass index, FFMI and BMD were similar in patients and controls, only 20% of patients had a healthy BMD compared with 50% of controls. Patients had reduced 6MWD and reported less physical activity (p < 0.05). Patients with bronchiectasis had increased arterial stiffness (an indicator of increased CV risk), increased inflammation, reduced exercise capacity and bone thinning. These additional comorbidities require further evaluation for their management in these patients.

Abstract: Summary Sarcoidosis affects the lungs in more than 90% of cases. Symptoms include cough, dyspnea, and chest pain. The entire respiratory tract can be involved. The most common areas of involvement are the airways and interstitium. Airway disease can lead to airway obstruction while interstitial lung disease can lead to restrictive disease. Patients may have a mix of these areas of involvement. For the symptomatic patient, the identification of disease involvement can usually be determined by pulmonary function testing and chest imaging. The chest X-ray staging system has been widely used in sarcoidosis, high-resolution computer tomography (HRCT) can provide detailed information regarding lung involvement. Unfortunately the various patterns seen on HRCT have limited the ability to develop a simple scoring system. Special studies such as bronchoscopy can be useful for detecting large airway disease. Other chest manifestations include adenopathy, pulmonary hypertension, and pulmonary muscle weakness. Fibrotic lung disease can lead to bronchiectasis, which can become infected. In this issue Everything you always wanted to know about sarcoidosis… but were afraid to ask D. Valeyre, Bobigny, France and M. Humbert, Kremlin-Bicetre, France Pathogenesis of Sarcoidosis J. Muller-Quernheim et al. Freiburg, Germany Pulmonary Manifestations of Sarcoidosis R.P. Baughman et al. Cincinnati, USA Pulmonary hypertension complicating sarcoidosis H. Nunes et al. Bobigny, France Cardiac sarcoidosis C. Chapelon-Abric, Paris, France Neurosarcoidosis: clinical manifestations, diagnosis and treatment K. Nozaki, Charleston, USA and M.A. Judson, Albany, USA Ocular sarcoidosis B. Bodaghi et al., Paris, France Skin manifestations of sarcoidosis J. Mana and J. Marcoval, Barcelona, Spain

Abstract: Lymphobronchial tuberculosis (TB) is tuberculous lymphadenopathy involving the airways, which is particularly common in children. To describe CT findings of lymphobronchial TB in children, the parenchymal complications and associated abnormalities. CT scans of children with lymphobronchial TB were reviewed retrospectively. Lymphadenopathy, bronchial narrowing, parenchymal complications and associations were documented. Infants comprised 51% of patients. The commonest site of lymphadenopathy was the subcarinal mediastinum (97% of patients). Bronchial compression was seen in all children (259 bronchi, of these 28% the bronchus intermedius) with severe or complete stenosis in 23% of affected bronchi. Parenchymal complications were present in 94% of patients, including consolidation (88%), breakdown (42%), air trapping (38%), expansile pneumonia (28%), collapse (17%) and bronchiectasis (9%), all predominantly on the right side (63%). Associated abnormalities included ovoid lesions, miliary nodules, pleural disease and intracavitary bodies. Airway compression was more severe in infants and most commonly involved the bronchus intermedius. Numerous parenchymal complications were documented, all showing right-side predominance.