Symptomatic unilateral idiopathic giant bullous emphysema : a case report.

BACKGROUND: Idiopathic Giant Bullous Emphysema (or Vanishing Lung Syndrome) is a rare condition which is usually associated with male gender, active smoking and underlying emphysematous disease. We present an unusual case of a giant bulla occurring in the absence of these risk factors. CASE PRESENTATION: A 54-year-old woman presented to the respiratory outpatient clinic with gradually worsening left sided chest discomfort, which was most marked during a recent flight. She had no significant dyspnoea or other symptoms. She had a remote 5-pack-year smoking history. Chest X-Ray revealed a large hyperlucent area in the left upper lobe. CT Thorax found this to be an isolated bulla occupying more than one-third of the hemithorax. The remaining lung parenchyma was normal. A diagnosis of Idiopathic Giant Bullous Emphysema was made. The patient was referred for VATS (Video-assisted thoracoscopic surgery) bullectomy which was carried out without complication. Her symptoms resolved completely following the operation. CONCLUSIONS: This is an unusual case of a solitary giant bulla occurring without major risk factors or underlying lung disease. VATS bullectomy was shown to be an effective therapeutic option, allowing re-expansion of compressed lung tissue and complete resolution of symptoms.

Practice Guidelines for Standards of Adult Sleep Medicine Services.

Sleep disorders, i.e. diseases that affect, disrupt or involve sleep, represent major challenges for physicians and healthcare systems worldwide. The high prevalence, the complexity and the health burden of sleep disorders demand the establishment of specific clinical sleep centres where adequate and efficient diagnosis and management of patients with such diseases can be provided. This document describes practice guidelines for standards of adult sleep medicine centres in Ireland. These guidelines are the result of a consensus procedure in which all committee members of the Irish Sleep Society (ISS) were involved. The scope of these guidelines is to define the requirements of sleep medicine services, in terms of personnel, facilities, equipment and procedures.

Nitrate-rich beetroot juice selectively lowers ambulatory pressures and LDL cholesterol in uncontrolled but not controlled hypertension: a pilot study.

BACKGROUND: Dietary nitrate has been shown to increase nitrate/nitrite levels in multiple populations, with potential blood pressure lowering effects. However, there are few reports among hypertensives. AIMS: We aimed to assess the effect of daily nitrate in subjects with controlled hypertension vs. uncontrolled hypertension. METHODS: On day 0, hypertensives wore an ambulatory BP monitor (ABPM) for 24 h and fasting blood was taken. Subjects then consumed concentrated beetroot juice (12.9 mmol nitrate) for 14 consecutive days. On day 14 subjects consumed their last nitrate dose after fasting blood was drawn and again had an ABPM for 24 h. RESULTS: According to baseline ABPM, 11 subjects had controlled BP while 8 had uncontrolled BP. There were similar, significant increases in serum nitrate/nitrite in both groups. We observed little change in BP variables among controlled hypertensives. However, there were reductions in BP variables in uncontrolled hypertensives where decreases in nighttime DBP (-6 ± 4.8 mmHg), arterial stiffness (-0.08 ± 0.03 ambulatory arterial stiffness index) and LDL (-0.36 ± 0.42 mmol/L) reached significance (p = 003, 0.05 and 0.046, respectively). CONCLUSIONS: Our results support the existing data suggesting an anti-hypertensive effect of nitrate-containing beetroot juice, but only among those with uncontrolled hypertension.

The Association Between 25 Hydroxyvitamin D and Airway Obstruction in Asthma.

Since Vitamin D has anti-inflammatory effects we wondered whether the association between low serum 25OHD and airway obstruction in moderate persistent asthma might be explained by inflammatory pathways that worsen asthma. All subjects examined were Irish Caucasians with moderate persistent asthma and none took systemic steroid therapy. In addition to computerized spirometry, we measured BMI, serum 25-hydroxyvitamin D (25OHD), total IgE, Eosinophil Cationic Protein (ECP), and high sensitive C- reactive protein (hs-CRP). One hundred (47 male) subjects completed the testing. Within single level of asthma severity, 25OHD levels were related to post-bronchodilator FEV1/FVC (r = 0.26, p< 0.01), but multiple linear regression analysis demonstrated that the association was not explained by obesity or inflammatory markers. We find a relationship exists between airway obstruction and 25OHD levels in asthmatic adults, and the effect is not explained by the presence of potential confounders such as obesity, allergy and systemic inflammation.

Isolated anterior mediastinal tuberculosis in an immunocompetent patient.

BACKGROUND: The differential diagnosis of a mediastinal mass is a common challenge in clinical practice, with a wide range of differential diagnosis to be considered. One of the rarer causes is tuberculosis. Atypical presentations of tuberculosis are well documented in immunocompromised patients, but should also be considered in the immunocompetent. CASE PRESENTATION: This case outlines a previously healthy 22 year-old immunocompetent male presenting with worsening chest pain, positional dyspnea, dry cough and dysphagia. Chest x-ray showed evidence of an isolated anterior mediastinal mass, which was confirmed on computed tomography. A mediastinoscopy was diagnostic as histology revealed necrotizing granulomatous inflammation and the presence of acid-fast bacilli, indicating mediastinal tuberculosis. CONCLUSION: Typically the underlying presentation of mediastinal tuberculosis is mediastinal lymphadenitis. This case was unusual in that we detected an isolated large anterior mediastinal mass accompanied by a relatively small burden of mediastinal lymphadenitis. Cases similar to this have been documented in immunosuppressed patients however in our case no evidence of immunosuppression was found. This case report emphasizes the importance that a detailed and logical pathway of investigation is pursued when encountering a mediastinal mass.

Current difficulties in the diagnosis and management of spinal tuberculosis.

BACKGROUND: The diagnosis of spinal tuberculosis (ST) is difficult and it commonly presents at an advanced stage. The management and follow up is complicated by a lack of guidance on the appropriate use and interpretation of spinal magnetic resonance studies (MR). AIMS: A retrospective study was performed at a UK centre to identify the demographic and presenting features of a spinal TB population, their response to treatment, and the value of follow up MR studies. PATIENTS AND RESULTS: Twenty one patients were identified with mean symptom duration of 11 (1.5-36) months having been assessed by a health practitioner on 3.2 (0-10) occasions before referral for investigation for ST. Twenty were born outside the UK. Their mean duration of residence in the UK was 6.67 (0.75-20) years, and six (32%) were resident for more than 10 years. Most (85.7%) did not have a medical history and one was HIV positive. Back pain, neurological, and constitutional symptoms were found in 100%, 29%, and 38% respectively. Musculoskeletal and neurological signs were found in 29% and 19% respectively. Spinal MR performed between 6 and 12 months suggests that six months of chemotherapy (for a fully sensitive organism) may not be sufficient to achieve disease resolution. CONCLUSIONS: Awareness of the demographic, clinical, and laboratory features of an ST population may facilitate earlier diagnosis. Guidance is required on the appropriate use and interpretation of MRI in the follow up of these patients.

Sleep disordered breathing and its treatment in congestive heart failure.

Sleep disordered breathing (SDB) is a common problem with adverse cardiorespiratory, endocrinological, and endothelial effects. Recent studies demonstrate an even higher prevalence of SDB in congestive heart failure (CHF) than in a randomly selected population, with up to 40% and 11% having Cheyne Stokes respiration-central sleep apnoea and obstructive sleep apnoea-hypopnoea syndromes, respectively. Randomised controlled trials of nocturnal respiratory support for SDB associated with CHF for up to three months demonstrate significant benefits in terms of improvements in left ventricular ejection fraction, markers of sympathetic system activity, and quality of life. Further randomised controlled trials of larger scale and longer duration are required to establish the role and benefit of this intervention for the treatment of this debilitating condition. The evidence for the higher prevalence of SDB in CHF, its pathogenesis, its pathophysiological consequences, and the emerging benefits of respiratory support are reviewed.

Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin hypersensitivity.

Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs) but there is no consensus on a standardized protocol. As a prior clinical history of adverse reactions to aspirin is poorly predictive of a positive result from formal aspirin challenge, many patients have an OAC performed. We retrospectively identified and prospectively validated how a 1-day OAC protocol could be modified, and patient selection improved, to deliver a safe and more efficient service. In a retrospective audit of 45 OACs using a 2 h dose interval, all reactions occurred within 90 min of the threshold dose. Forty OACs were then performed using a 90-min dose interval. This reduced the mean duration of a positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively. Histories of multiple manifestations of AHs were found in 91.6% (11) of those with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6% (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5% (1) with angiooedema, with a positive OAC, had a history of a single manifestation of AHs. The efficiency of an OAC service can safely be improved by reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient selection, as the likelihood of a positive OAC increases among patients with a history of asthma, angiooedoema or anaphylaxis with multiple manifestations of AHs.

Multiple system atrophy presenting as central sleep apnoea.

A 61-yr-old male presented with apparent idiopathic central sleep apnoea but after 4 yrs developed features of autonomic, cerebellar and extrapyramidal dysfunction consistent with a diagnosis of multiple system atrophy (MSA). Though central sleep apnoea can occur in multiple sleep apnoea, it is less frequent than obstructive sleep apnoea and occurs in the later stages of the disease. The pathogenesis of MSA involves gliosis and neuronal cell loss in specific areas of the central nervous system. Central sleep apnoea in MSA may be due to the depletion of cholinergic neurons in the arcuate nucleus of the medulla by apoptosis. This is the first description of multiple system atrophy presenting as central sleep apnoea. The current authors believe that multiple system atrophy should be considered in the differential diagnosis of late onset central sleep apnoea and progressive hypoventilation.

Fluticasone induces T cell apoptosis in the bronchial wall of mild to moderate asthmatics.

BACKGROUND: Cytokines which signal via the gamma chain of the interleukin (IL)-2 receptor and the interferons (IFNs) have been shown to enhance T cell survival in vitro by rescuing cells from apoptosis. METHODS: A study was undertaken to determine whether treatment with inhaled fluticasone propionate (FP; 250 microg twice daily) for 2 weeks could modulate production of IL-15 or IFN-beta and thereby affect T cell survival in bronchial tissue of 10 patients with mild/moderate asthma. Bronchial biopsy specimens were taken before and on completion of treatment. RESULTS: The mean (95% CI) number of T cells per unit area decreased in the asthmatic group following 2 weeks of treatment with FP (from 7.0 (5.6 to 8.4) to 4.5 (4.0 to 5.1); p = 0.001). There was an increase in the percentage of T cells undergoing apoptosis following FP treatment as assessed by T cell/TUNEL staining (from 4.5 (2.6 to 6.4) to 8.7 (6.6 to 10.8); p = 0.0001). The percentage of cells staining for IL-15 and IFN-beta in the lamina propria, determined by an alkaline phosphatase biotin streptavidin technique, decreased significantly from baseline values of 31.6 (23.4 to 39.7) to 19.6 (12.5 to 26.7), p = 0.039 for IL-15 and from 18.9 (13.5 to 24.4) to 9.5 (5.9 to 13.1), p = 0.007 for IFN-beta following 2 weeks of treatment with FP. However, only the decrease in the percentage of cells staining for IL-15 was significantly correlated with an increased number of apoptotic T cells following treatment (p = 0.008). CONCLUSION: These findings support a novel mechanism for the ability of inhaled corticosteroids to decrease T cell numbers, possibly by downregulation of the cytokine IL-15.

Rocking bed and prolonged independence from nocturnal non-invasive ventilation in neurogenic respiratory failure associated with limb weakness.

A 40 year old mother of three with autosomal dominant scapuloperoneal muscular dystrophy presented with severe neurogenic respiratory failure requiring nocturnal non-invasive ventilation (NIV). Because of the development of profound proximal muscular weakness as a consequence of the progressive nature of her neurological disease, she eventually was unable to apply and remove the facial interface to set up her NIV circuit. She therefore became dependent on her children and carers to start and stop NIV during the night. A rocking bed was successfully employed as an alternative to nocturnal NIV. Ventilation was facilitated by the passive movement of the diaphragm as a consequence of the movement of the abdominal contents under the effect of gravity. Benefit was demonstrated objectively by pulse oximetry and subjectively by the improvement in the patient's symptomatology and continued independence at night. The ease of use of a rocking bed should be borne in mind when the necessity for nocturnal ventilatory support in neuromuscular disease results in the potential loss of independence for a patient.

G-CSF enables completion of tuberculosis therapy associated with iatrogenic neutropenia.

Neutropenia is a rare complication of anti-tuberculous therapy and is usually due to a single agent, most frequently isoniazid. The current case describes a previously healthy immunocompetent patient with tuberculosis of the lymph nodes who developed neutropenia due to a number of first line antibiotics (rifampicin, isoniazid and ethambutol) and streptomycin when introduced in combination and individually thus resulting in repeated treatment disruption. The introduction of twice-weekly subcutaneous granulocyte-colony stimulating factor to correct iatrogenic neutropenia facilitated the continuation and eventual completion of therapy without adverse effect. This is the first description of the use of granulocyte-colony stimulating factor to correct iatrogenic neutropenia due to anti-tuberculous antibiotics and the second description of the occurrence of iatrogenic neutropenia to more than anti-tuberculous antibiotic in an individual.

Activated, cytotoxic CD8(+) T lymphocytes contribute to the pathology of asthma death.

This study investigates the presence of CD8(+) T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8(+) cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8(+) cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 +/- 1.92% versus 3.93 +/- 1.63% and 1.09 +/- 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 +/- 1.5%) compared with 1.39 +/- 0.9; 1.8 +/- 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN-gamma) by CD8(+) T cells was higher in the AD group than the control group (p < 0.05). Furthermore, the IFN-gamma/IL-4 ratio in the AD group was less than half that of the control group (1.46 +/- 0.2 versus 3.2 +/- 0.1; p = 0.02). Using polymerase chain reaction (PCR), viral genome for rhinovirus (RV) was detected in lung tissue from three of the seven cases in the AD group. Two of these cases also had detectable respiratory syncytial virus (RSV). Viral genome for RSV was detected in five of the AUC group and in one of these cases, RV was also detected. No viral genome was detected in the lungs of the control group. In conclusion, this study provides novel evidence of an aberrant CD8(+) T-cell population, possibly in response to viral infection in subjects who die of acute asthma.

IFN-gamma but not IL-4 T cells of the asthmatic bronchial wall show increased incidence of apoptosis.

BACKGROUND: Previous observations have established that IFN-gamma production is depressed in CD4+ T cells from atopic asthmatics compared with non-asthmatics. OBJECTIVE: The aim of this study was to determine if decreased IFN-gamma production could be due to a dissociation between levels of apoptosis within the T cell subsets of the asthmatic bronchial wall. METHODS: Twenty asthmatics (10 atopic and 10 non-atopic) and eight non-atopic non-asthmatics underwent bronchoscopy. Cryostat sections of these biopsies were investigated using immunohistological techniques to determine the relative number of CD4/FAS+ and CD4/Bcl-2+ cells. Detection of IFN-gamma+ and IL-4+ was combined with TUNEL staining to determine the proportions of the Th1 and Th2 cells undergoing apoptosis. RESULTS: Experiments revealed raised proportions of activated CD4+ T cells as assessed by expression of HLA-DR and CD25+ expression in the asthmatic samples. Expression of Bcl-2 by the CD4+ cell population was significantly reduced in the asthmatic compared with the control group (P = 0.002). There was no significant difference in the expression of CD4+ Fas-ligand or the number of CD4+ undergoing apoptosis in the asthmatic and non-asthmatic groups. However, the IFN-gamma+ (P = 0.04) but not IL-4+ T cells in the asthmatic biopsies had significantly higher proportions of apoptotic cells compared with the control group. CONCLUSION: The evidence supports the hypothesis that Th1/Th2 imbalance in asthmatic inflammation may be a result of premature apoptosis within the Th1 subset.