ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia.

Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.

Type IV delayed-type hypersensitivity of the respiratory tract due to budesonide use: report of two cases and a literature review

Respiratory type-IV hypersensitivity reactions due to corticosteroids is a rare phenomenon. We describe two such cases. The first is a 37- year-old atopic woman who developed labial angioedema and nasal itching after the use of budesonide nasal spray. A month later, after the first puffs of a formoterol/budesonide spray prescribed for asthma, she noticed symptoms of tongue and oropharyngeal itching and redness with subsequent dysphagia, labial and tongue angioedema, and facial oedema. The second is a 15-year-old non-atopic woman who reported pruritic eruptions around the nostrils after using a budesonide nasal spray. A year later she presented with nasal pruritus with intense congestion and labial and facial oedema after using the same spray. Both patients were evaluated with patch-tests using the commercial T.R.U.E. test, a budesonide solution, and corticosteroid creams. Test evaluation was performed at 48 and 96 hours. In both patients, patch tests were positive to budesonide (++) on the second day. The first patient also had a positive (+) reaction to tixocortol-21-pivalate. All the other patch tests were negative. Clinicians should be aware that hypersensitivity reactions may occur during the use of nasal or inhaled corticosteroids.

Immunofluorescence versus xTAG multiplex PCR for the detection of respiratory picornavirus infections in children

BACKGROUND: Polymerase chain reaction (PCR) is a sensitive tool for detection of respiratory picornaviruses. However, the clinical relevance of picornavirus detection by PCR is unclear. Immunofluorescence (IF), widely used to detect other respiratory viruses, has recently been introduced as a promising detection method for respiratory picornaviruses. OBJECTIVES: To compare the clinical manifestations of respiratory picornavirus infections detected by IF with those of respiratory picornavirus infections detected by xTAG multiplex PCR in hospitalized children. STUDY DESIGN: During a 1-year period, nasopharyngeal aspirates (NPA) from all children hospitalized due to an acute respiratory infection were prospectively analyzed by IF. All respiratory picornavirus positive IF samples and 100 IF negative samples were further tested with xTAG multiplex PCR. After exclusion of children with co-morbidities and viral co-infections, monoinfections with respiratory picornaviruses were detected in 108 NPA of 108 otherwise healthy children by IF and/or PCR. We compared group 1 children (IF and PCR positive, n=84) with group 2 children (IF negative and PCR positive, n=24) with regard to clinical manifestations of the infection. RESULTS: Wheezy bronchitis was diagnosed more often in group 1 than in group 2 (71% vs. 46%, p=0.028). In contrast, group 2 patients were diagnosed more frequently with pneumonia (17% vs. 6%, p=0.014) accompanied by higher levels of C-reactive protein (46mg/l vs. 11mg/l, p=0.009). CONCLUSIONS: Picornavirus detection by IF in children with acute respiratory infection is associated with the clinical presentation of wheezy bronchitis. The finding of a more frequent diagnosis of pneumonia in picornavirus PCR positive but IF negative children warrants further investigation.

Topical curcumin can inhibit deleterious effects of upper respiratory tract bacteria on human oropharyngeal cells in vitro: potential role for patients with cancer therapy induced mucositis?

Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis.

Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure

Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome.

The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure

This case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO(2)/FiO(2)) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO(2), 26-42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12-15 mmHg; FiO(2), 0.8-1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO system for 8-11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO(2)/FiO(2) ratio and EVLW were performed. A significant correlation between EVLW and the PaO(2)/FiO(2) ratio (Spearman-rho correlation coefficient, -0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.

Pros and cons of post-mortem CT imaging on aspiration diagnosis

Recently, the field of forensics has experienced a rapid increase in the use of modern cross-sectional imaging in forensic investigations. We examined the value of post-mortem computed tomography (CT) imaging relative to autopsy for distinguishing aspiration into the lungs from airways, from lung alterations due to other causes, and for identifying the aspirated material. We selected 54 bodies submitted to whole-body CT scanning prior to autopsy. All cases had autopsy findings of blood (31 cases), fresh water (12 cases), or gastric content (11 cases) aspiration. The radiological images were retrospectively analyzed for airway and lung aspiration. In all cases, CT imaging detected pulmonary abnormalities suggestive of aspiration. Nevertheless, analysis of the CT images alone was not able to identify the aspirated material or to distinguish pulmonary findings of aspiration from lung changes due to other causes, except for a few cases of hemo-aspiration. However, due to its ability to visualize the entire parenchyma, CT imaging was superior to autopsy in providing additional data about the distribution and severity of the aspiration as well as in detecting small abnormalities. Post-mortem CT imaging should be considered as a superior tool for forensic investigations of aspiration due to its ability to document diagnostic conclusions and to guide the forensic pathologist during lung tissue examination.

Blood aspiration as a vital sign detected by postmortem computed tomography imaging

Blood aspiration is a significant forensic finding. In this study, we examined the value of postmortem computed tomography (CT) imaging in evaluating findings of blood aspiration. We selected 37 cases with autopsy evidence of blood in the lungs and/or in the airways previously submitted to total-body CT scanning. The CT-images were retrospectively analyzed. In one case with pulmonary blood aspiration, biopsy specimens were obtained under CT guide for histological examination. In six cases, CT detected pulmonary abnormalities suggestive of blood aspiration, not mentioned in the autopsy reports. CT reconstructions provided additional data about the distribution and extent of aspiration. In one needle-biopsied case, the pulmonary specimens showed blood in the alveoli. We suggest the use of CT imaging as a tool complementary to traditional techniques in cases of blood aspiration to avoid misdiagnosis, to guide the investigation of lung tissue, and to allow for more evidence-based inferences on the cause of death.

Monocyte differentiation toward regulatory dendritic cells is not affected by respiratory syncytial virus-induced inflammatory mediators

Airway epithelial cells were shown to drive the differentiation of monocytes into dendritic cells (DCs) with a suppressive phenotype. In this study, we investigated the impact of virus-induced inflammatory mediator production on the development of DCs. Monocyte differentiation into functional DCs, as reflected by the expression of CD11c, CD123, BDCA-4, and DC-SIGN and the capacity to activate T cells, was similar for respiratory syncytial virus (RSV)-infected and mock-infected BEAS-2B and A549 cells. RSV-conditioned culture media resulted in a partially mature DC phenotype, but failed to up-regulate CD80, CD83, CD86, and CCR7, and failed to release proinflammatory mediators upon Toll-like receptor (TLR) triggering. Nevertheless, these DCs were able to maintain an antiviral response by the release of Type I IFN. Collectively, these data indicate that the airway epithelium maintains an important suppressive DC phenotype under the inflammatory conditions induced by infection with RSV.

Respiratory muscle activity related to flow and lung volume in preterm infants compared with term infants

Infants with chronic lung disease (CLD) have a capacity to maintain functional lung volume despite alterations to their lung mechanics. We hypothesize that they achieve this by altering breathing patterns and dynamic elevation of lung volume, leading to differences in the relationship between respiratory muscle activity, flow and lung volume. Lung function and transcutaneous electromyography of the respiratory muscles (rEMG) were measured in 20 infants with CLD and in 39 healthy age-matched controls during quiet sleep. We compared coefficient of variations (CVs) of rEMG and the temporal relationship of rEMG variables, to flow and lung volume [functional residual capacity (FRC)] between these groups. The time between the start of inspiratory muscle activity and the resulting flow (tria)--in relation to respiratory cycle time--was significantly longer in infants with CLD. Although FRC had similar associations with tria and postinspiratory activity (corrected for respiratory cycle time), the CV of the diaphragmatic rEMG was lower in CLD infants (22.6 versus 31.0%, p = 0.030). The temporal relationship of rEMG to flow and FRC and the loss of adaptive variability provide additional information on coping mechanisms in infants with CLD. This technique could be used for noninvasive bedside monitoring of CLD.

Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. Methods Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. Results Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score. Conclusions Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.