Patterns of Disease in Patients with Middle-Lobe Predominant Bronchiectasis.

BACKGROUND: Middle-lobe predominant bronchiectasis affecting the right middle-lobe and/or lingula (RMLP) is classically described in asthenic, elderly females with skeletal abnormalities or associated nontuberculous mycobacterial (NTM) infection. OBJECTIVES: We aimed to evaluate the frequency and clinical characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed bronchiectasis patients and determine associations with disease severity. METHODS: A retrospective observational cross-sectional cohort study of consecutive bronchiectasis patients in our institution was performed. Data were collected on baseline variables, microbiology status, lung function, and radiology according to the modified Bhalla score. Disease severity was assessed using bronchiectasis severity index (BSI) and FACED severity scores. RESULTS: Of 81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20 (24.7%) had RMLP disease. These patients were significantly younger, female, and with lower BMIs than patients with the classical bronchiectasis phenotype (p = 0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum (p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in RMLP patients were significantly lower than their counterparts (both p < 0.001). CONCLUSIONS: The RMLP phenotype is associated with younger patients than classically described in the literature. An increased rate of NTM infection in this phenotype was noted, particularly in females, but much lower than previously described. Lung function and disease severity scores in this patient group are relatively normal, suggesting a milder phenotype in patients with this form of the disease.

Effect of chemotherapy on quality of life in patients with non-small cell lung cancer.

PURPOSE: This study was conducted to evaluate the extent to which quality of life (QoL) assessment has been incorporated into clinical trials of patients with advanced non-small cell lung cancer (NSCLC) receiving palliative chemotherapy. PATIENTS AND METHODS: Phase III trials for patients with NSCLC treated with palliative chemotherapy were identified by a literature search of PubMed. All abstracts and relevant articles from August 1986 to October 2011 were reviewed. The primary focus was on (a) whether these articles had incorporated QoL as an endpoint, (c) what instruments were used to measure QoL and (c) impact of chemotherapy on QoL. RESULTS: There were 3,780 items indexed under 'quality of life and lung cancer'. One hundred three studies were identified which measured QoL using validated QoL instruments. Fifty-five of these trials assessed the effects of palliative chemotherapy on QoL in patients with advanced NSCLC. The European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire was the most widely used questionnaire; other commonly used measurement scales used were the Functional Assessment of Cancer Therapy-Lung and the Lung Cancer Symptom Scale. The majority of studies showed that chemotherapy had a positive impact on QoL and disease-specific symptoms. CONCLUSION: It is now widely accepted that QoL should be considered as a primary endpoint of treatment in patients with advanced lung cancer both in clinical practice and clinical trials to further define meaningful response. As the traditional outcome measures of survival and tumour response are poor in this population, QoL assessment may offer a more comprehensive approach to evaluating the relative risks and benefits associated with treatments.

A grossly abnormal trachea- severe tracheal diverticulosis and Mounier-Kuhn syndrome.

A 53-year-old smoker presented with a history of recurrent lower respiratory tract infections. A diagnosis of Tracheal Diverticulosis due to Tracheobronchomegaly (Mounier-Kuhn Syndrome) was made. The clinical history, diagnosis and treatment options are discussed.

Randomised controlled trial of the effect of standard and detailed risk disclosure prior to bronchoscopy on peri-procedure anxiety and satisfaction.

BACKGROUND: Deciding what risks to disclose before a procedure is often challenging for clinicians. Consecutive patients undergoing elective fibreoptic bronchoscopy were randomised to receive simple or more detailed written information about the risks of the procedure and the effects on anxiety and satisfaction levels were compared. METHODS: A 100 mm anxiety visual analogue scale (VAS) and a modified Amsterdam preoperative anxiety (scored 4-20) scale (APAIS) were completed before and after reading the designated information leaflet. Following bronchoscopy, subjects completed a satisfaction questionnaire. RESULTS: Of 142 consecutive patients, 122 (86%) (mean age 57.8 years, 53% male) completed the study. Baseline demographic, clinical and anxiety measures were similar in the two groups. Those who received more detailed risk information had significantly greater increase in anxiety levels than those who received simple information on both the VAS (mean 14.0 (95% CI 10.1 to 17.9) vs 2.5 (95% CI -1.4 to 6.4), p<0.001) and the APAIS (1.73 (95% CI 1.19 to 2.26) vs 0.57 (95% CI 0.05 to 1.10), p<0.001). Almost twice as many of those receiving detailed risk information reported that they felt they had received too much information about complications or that the information they had received about bronchoscopy had been worrying. CONCLUSIONS: Provision of more detailed risk information before bronchoscopy may come at the cost of a small but significant increase in anxiety.

Predictive value of C-reactive protein and clinically relevant baseline variables in sarcoidosis.

BACKGROUND: This study aims to examine the predictive and prognostic implications of C-reactive protein (CRP) and clinically relevant baseline variables in determining treatment indication and disease progression in a large clinical cohort of patients with stable sarcoidosis. METHODS: A retrospective observational study of 328 sarcoidosis patients attending a regional tertiary referral centre over a 26-year period was performed. Clinical, biochemical, radiological and physiological data were analysed according to a clinically relevant dichotomous cutpoint of CRP. Multiple models of logistic regression were used to determine independent predictors of outcome as defined by indication for treatment with corticosteroids, radiological deterioration and physiological progression. RESULTS: 328/409 (80.2%) sarcoidosis patients had baseline serum CRP measured and were suitable for inclusion. Baseline CRP was elevated in 154 (47%). 178 (54.3%) were prescribed corticosteroid treatment during the disease course. Physiological deterioration was demonstrated in 48 (14.6%) patients and radiological progression in 59 (17.9%) patients. High baseline CRP was strongly associated with Lofgren's syndrome (p=<0.001) and reduced FVC% predicted (p=0.012). High CRP was found to be a negative predictor of radiological progression (p=0.046). In a sub-analyses of patients without Lofgren's syndrome (n=223), patients with high baseline CRP were almost twice as likely to receive corticosteroid treatment, OR 1.89 (95% CI 1.04-3.55). Low baseline DLCO% independently predicted the need for corticosteroid treatment (p=<0.001) and physiological decline (p=0.045). CONCLUSIONS: Elevated baseline CRP in sarcoidosis is associated with a good prognosis and is a negative predictive indicator of radiological progression. In patients without Lofgren's syndrome, high CRP and low DLCO% at presentation may identify a subset of patients more likely to develop physiological progression who may benefit from early systemic treatment.

Advance directives for truth disclosure.

INTRODUCTION: Although most patients wish to be fully informed about bad news such as a diagnosis of cancer, a significant minority prefer no or minimal information. We examined the value of asking patients about their disclosure preferences at the outset of hospitalization. METHODS: Consecutive patients admitted to a respiratory and a geriatric unit were asked whether and how they would wish to be told of cancer or Alzheimer disease. RESULTS: Of the 207 patients interviewed, 174 (84%) wanted to be told about cancer or dementia; the proportion who would wish to be told did not differ between older patients (89 of 108 patients; 82%) and younger patients (85 of 99 patients; 86%; p = 0.34). Thirty patients (15%) sought reassurance during or after the interview, and 13 patients (6%) reported that they had been bothered by the questions. Of the 207 patients, cancer or dementia was diagnosed in 23 patients (11%). Preferences for disclosure or nondisclosure were honored for 20 patients (87%). CONCLUSIONS: Seeking preferences regarding truth disclosure at the outset of hospitalization is helpful and feasible in everyday practice, and the results can be used by clinicians to improve communication with patients and families in accordance with patients' own wishes.

Abdominal muscle use during breathing in unanesthetized dogs.

The pattern of abdominal muscle use during breathing in unanesthetized dogs is unknown. Therefore, we have recorded the electromyograms of the rectus abdominis, external oblique, and transversus abdominis in eight conscious animals breathing quietly in the sitting, standing, and prone postures. During quiet breathing in the sitting posture, all animals invariably had a large amount of phasic expiratory activity in the transversus abdominis. In contrast, only four animals showed some expiratory activity in the external oblique, and only one animal had expiratory activity in the rectus abdominis. A similar pattern was observed when the animals were standing or lying prone, although the amount of expiratory activity was less in this posture. Bilateral cervical vagotomy in four animals did not affect the degree of transversus abdominis expiratory activation or the influence of posture. We conclude that in conscious dogs 1) the abdominal muscles play an important role during breathing and make spontaneous quiet expiration a very active process, 2) the transversus abdominis is the primary respiratory muscle of the abdomen, and 3) unlike in anesthetized animals, extrapulmonary receptors play a major role in promoting abdominal expiratory contraction.

Triangularis sterni muscle use in supine humans.

The electrical activity of the triangularis sterni (transversus thoracis) muscle was studied in supine humans during resting breathing and a variety of respiratory and nonrespiratory maneuvers known to bring the abdominal muscles into action. Twelve normal subjects, of whom seven were uninformed and untrained, were investigated. The electromyogram of the triangularis sterni was recorded using a concentric needle electrode, and it was compared with the electromyograms of the abdominal (external oblique and rectus abdominis) muscles. The triangularis sterni was usually silent during resting breathing. In contrast, the muscle was invariably activated during expiration from functional residual capacity, expulsive maneuvers, "belly-in" isovolume maneuvers, static head flexion and trunk rotation, and spontaneous events such as speech, coughing, and laughter. When three trained subjects expired voluntarily with considerable recruitment of the triangularis sterni and no abdominal muscle activity, rib cage volume decreased and abdominal volume increased. These results indicate that unlike in the dog, spontaneous quiet expiration in supine humans is essentially a passive process; the human triangularis sterni, however, is a primary muscle of expiration; and its neural activation is largely coupled with that of the abdominals. The triangularis sterni probably contributes to the deflation of the rib cage during active expiration.

Non invasive study of left ventricular function in chronic renal failure before and after hemodialysis.

Eight patients with chronic renal failure, who were on chronic hemodialysis were studied. The systolic time intervals were measured from simultaneous recordings of the electrocardiogram, phonocardiogram and carotid arterial pulse tracing. The ventricular volumes and stroke volume were calculated from echocardiographic recordings. The following indices of contractility were derived from the echocardiographic traces - the mean circumferential fiber shortening rate (mean VCF), and mean posterior wall velocity (PWV), mean normalized posterior wall velocity (VPW), and mean normalized interventricular septal velocity (VIVS). The studies were performed immediately before and after a routine dialysis. All the patients had abnormal end diastolic volumes in the basal state. After dialysis the end diastolic volume, stroke volume and left ventricular ejection time were reduced significantly. These changes in cardiac pump function reflect the post dialysis reduction of blood volume. The values for the contractility indices all improved after dialysis and this change correlates well with the abbreviation of left ventricular ejection time (r = .92). It is concluded that the main effects of dialysis are on pump function, and although the changes in the normalized velocities may indicate a real improvement in contractility, their validity is limited by their dependence on left ventricular load conditions and ejection time. Echocardiographic determination of ejection fraction and mitral valve E point - septal separation are suggested as reliable indices of cardiac pump function.

Functional genomics in sarcoidosis--reduced or increased apoptosis?

BACKGROUND: A variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signaling pathways. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in patients with acute onset sarcoidosis. METHOD: We have performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HGU95A, Affymetrix) for RNA expression profiling from peripheral blood mononuclear cells from patients with acute pulmonary sarcoidosis and matched healthy controls. Twelve patients and 12 controls were assessed, mean age 36 +/- 12 and 33 +/- 10 years respectively. Results focus on apoptosis-related gene products. Group differences were assessed with the Mann-Whitney U-test. RESULTS: Seven patients had self-limited disease (all type I sarcoidosis) and 5 progressive disease requiring immunosuppression (all type II or III sarcoidosis). We found 53 of 112 (47%) apoptosis-related gene products dysregulated in sarcoidosis compared to controls. Particular growth factors, especially heparin-binding EGF-like GF, EGF, PDEGF, SISPDGF2 and VEGF, were upregulated in patients consistent with a pro-survival profile. The Bcl-2 family of genes also showed a net pro-survival profile in sarcoidosis patients. In contrast, alterations in the TNF-pathway were compatible with increased apoptosis signals in both, type I and type II/III sarcoidosis patients. Other cell death receptors were equally expressed, as were caspases and p53-associated genes. In contrast to patients with type I-sarcoidosis, patients with progressive type II or III disease showed an upregulation of NFKB and a leak of downregulation of inhibitor of apoptosis 1. CONCLUSION: Significant differences in the expression of apoptosis-related genes were found in peripheral blood of patients with acute onset sarcoidosis. Gene expression did not show a definite pattern that was suggestive of pro-survival or proapoptosis. However, the number of genes whose altered expression would be predicted to favour increased survival exceeded that of genes likely to reduce survival. Protein-based confirmation of the differences in the activity of apoptosis-pathways needs to be done in further studies.

Combination chemotherapy in the treatment of inoperable non-small cell lung cancer.

BACKGROUND: Chemotherapy is an established intervention in inoperable non-small cell lung cancer (NSCLC), yet few Irish patients receive this treatment. AIM: To determine survival, toxicity and radiological response following chemotherapy for NSCLC at our institution. METHODS: Retrospective audit of all patients receiving chemotherapy for histologically proven, inoperable NSCLC from January 1997 to December 2000. RESULTS: There were 80 treatment episodes in 77 patients, mean age 62 years. Forty-eight (60%) patients had locally advanced and 32 (40%) metastatic disease. Mitomycin, Ifosfamide, Carboplatin (MIC) and Paclitaxel/Carboplatin (PC) were the most commonly administered regimens. Median survival for locally advanced and metastatic disease was 13.9 months and 7.1 months respectively. Severe neutropenia and thrombocytopenia were each witnessed after less than 9% of cycles. Eleven (16.7%) patients had radiological response including 4 (6.1%) complete responses. CONCLUSION: Survival for inoperable NSCLC treated with chemotherapy was encouraging and achieved at low toxicity.

Dramatic response to nebulized morphine in an asthmatic patient with severe chronic cough.

We report a 56 year old man with a 16 year history of bronchial asthma who suffered severe coughing spasms that prevented employment, greatly reduced exercise tolerance and caused profound social embarrassment. His cough failed to respond to all standard asthma therapy and nebulized lignocaine. The patient was commenced on nebulized morphine sulphate with dramatic reduction in cough and improved quality of life. This benefit has been maintained at 2.5 years of follow-up.

Pulmonary alveolar proteinosis: report of two cases in the West of Ireland with review of current literature.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare lung condition characterised by the accumulation of lipoproteinaceous surfactant material within alveolar airspaces resulting in clinical manifestations ranging from asymptomatic to severe respiratory failure. Three disease subtypes are recognised: autoimmune, secondary and congenital. METHODS: We describe two presentations of PAP in the West of Ireland with a review of the current literature. RESULTS: Autoimmune PAP, associated with the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies, accounts for >90 % of cases. Treatment with whole lung lavage is the current standard of care. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) and anti-GM-CSF antibodies (rituximab, plasmapharesis) are under investigation. CONCLUSIONS: This is a summary of available literature outlining current clinical practice in the diagnosis, management, and treatment of PAP. PAP should be considered in the differential diagnosis of any patient with a restrictive pulmonary defect. Without high clinical suspicion, this diagnosis can easily be missed.

Bilateral micronodular pulmonary infiltrate: is it important to make a histological diagnosis?

Pulmonary alveolar microlithiasis is a rare disease characterized by the deposition of calcium phosphate within the alveoli. We report the case of a 20-year-old man with a 6-week history of cough and shortness of breath on exertion. The chest radiograph demonstrated a bilateral symmetrical micronodular pattern. High-resolution computed tomography revealed bilateral diffuse fine nodular shadowing involving the mid zones, with sparing of the apices. The patient underwent a transbronchial lung biopsy, which confirmed the diagnosis of pulmonary alveolar microlithiasis.

First presentation of sarcoidosis with severe obstructive sleep apnoea and epiglottic involvement.

Sarcoidosis of the upper respiratory tract (SURT) is rare but well documented. We present a patient whose first presentation with sarcoidosis was with dysphonia, upper airways obstruction and severe obstructive sleep apnoea (OSA) . Systemic steroids and hydroxycholoroquine led to improvement in phonation, endoscopic appearance and upper airway obstruction with significant improvement in Apnoea Hypopnoea Index (AHI) on polysomnography.

Solitary fibrous tumours of the pleura: report of two cases and literature review.

BACKGROUND: Solitary fibrous tumours of the pleura (SFTPs) are rare pleural mesenchymal neoplasms with distinct clinicopathological and immunohistochemical features, accounting for less than 5 % of all neoplasms involving the pleura. METHODS: We present two cases of SFTP with a review of the current literature. RESULTS: Clinical presentation varies according to size and intrathoracic localisation. The molecular pathology of SFTPs is largely unknown. Complete surgical resection is recommended with long-term clinic and radiographic follow-up due to its malignant potential. CONCLUSIONS: This is a summary of available literature outlining current clinical practice in the diagnosis, management, and treatment of SFTPs in Ireland.

Iron status and chronic kidney disease predict restless legs syndrome in an older hospital population.

BACKGROUND: Iron deficiency is important in the pathogenesis of restless legs syndrome (RLS), and serum ferritin measurement, using a cutoff of 45-50ng/ml, is widely recommended as the optimal screening test for iron deficiency in RLS. Serum ferritin often increases with inflammation, and a higher cutoff may be better in those with acute and chronic inflammatory conditions, including those with chronic kidney disease (CKD). METHODS: The relationships between RLS and potential secondary causes were examined in hospital patients aged 50years or more. Diagnosis of RLS was based on a clinician interview. RESULTS: Of 301 patients, 55 (18.3%) had RLS. Ferritin levels less than 40ng/ml and between 40 and 69ng/ml and Stage 4 CKD (estimated glomerular filtration rate [eGFR] between 15 and 29ml/min and not on dialysis) were associated with significantly higher odds for RLS in univariate and multivariate analyses. CONCLUSION: Iron deficiency and chronic kidney disease are the strongest predictors of RLS in older hospital patients. Ferritin less than 70ng/ml is the best cutoff for identifying possible iron deficiency in RLS patients with inflammatory conditions. Independent of iron status, RLS is strongly associated with chronic kidney disease that is not severe enough to require dialysis, and the results of this study suggest that eGFR values and stages of CKD should be reported in future studies of RLS.

Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs.

BACKGROUND: Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma. AIMS: The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication. METHODS: This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients. RESULTS: Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p < 0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 ± 0.41 to 0.8 ± 0.37 and the mean number of bed days occupied was reduced from 16.6 ± 2.94 to 5.3 ± 2.57 days, p < 0.001. The number of oral corticosteroid doses used fell from 3.1 ± 0.27 to 1.2 ± 0.17, p < 0.001. The overall cost saving per omalizumab responder patients for 6 months was 834. CONCLUSIONS: Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.