Elahna Paul

Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease

BACKGROUND Methods of classifying chronic obstructive pulmonary disease (COPD) depend largely upon spirometric measurements but disability is only weakly related to measurements of lung function. With the increased use of pulmonary rehabilitation, a need has been identified for a simple and standardised method of categorising disability in COPD. This study examined the validity of the Medical Research Council (MRC) dyspnoea scale for this purpose. METHODS One hundred patients with COPD were recruited from an outpatient pulmonary rehabilitation programme. Assessments included the MRC dyspnoea scale, spirometric tests, blood gas tensions, a shuttle walking test, and Borg scores for perceived breathlessness before and after exercise. Health status was assessed using the St George’s Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ). The Nottingham Extended Activities of Daily Living (EADL) score and Hospital Anxiety and Depression (HAD) score were also measured. RESULTS Of the patients studied, 32 were classified as having MRC grade 3 dyspnoea, 34 MRC grade 4 dyspnoea, and 34 MRC grade 5 dyspnoea. Patients with MRC grades 1 and 2 dyspnoea were not included in the study. There was a significant association between MRC grade and shuttle distance, SGRQ and CRQ scores, mood state and EADL. Forced expiratory volume in one second (FEV1) was not associated with MRC grade. Multiple logistic regression showed that the determinants of disability appeared to vary with the level of disability. Between MRC grades 3 and 4 the significant covariates were exercise performance, SGRQ and depression score, whilst between grades 4 and 5 exercise performance and age were the major determinants. CONCLUSIONS The MRC dyspnoea scale is a simple and valid method of categorising patients with COPD in terms of their disability that could be used to complement FEV1 in the classification of COPD severity.

Randomized controlled trial of pulmonary rehabilitation in severe chronic obstructive pulmonary disease patients, stratified with the MRC dyspnoea scale

This study tested the hypothesis that severity of respiratory disability may affect the outcome of pulmonary rehabilitation. In this randomized, controlled study, 126 patients with chronic obstructive pulmonary disease (COPD) were stratified for dyspnoea using the Medical Research Council (MRC) dyspnoea score into MRC3/4 (Moderate) (n=66) and MRC 5 (Severe) dyspnoeic (n=60) groups. The patients were randomly assigned to an eight week programme of either exercise plus education (Exercise group) or education (Control group). Education and exercise programmes for the moderately dyspnoeic patients were carried out in a hospital outpatient setting. Severely dyspnoeic patients were all treated at home. Those in the Exercise group received an individualized training programme. There was a significant improvement in shuttle walking distance in the moderate dyspnoeic group, who received exercise training; baseline (mean+/-SEM) 191+/-22 m, post-rehabilitation 279+/-22 m (p<0.001). There was no improvement in exercise performance in the severely dyspnoeic patients receiving exercise. Neither group of control patients improved. Health status, assessed by the Total Chronic Respiratory Disease Questionnaire score, increased in the moderately dyspnoeic patients receiving exercise from 80+/-18 to 95+/-17 (p<0.0001) after rehabilitation. Much smaller changes were seen in the other three groups. Improvement in exercise performance and health status in patients with chronic obstructive pulmonary disease after an exercise programme depends on the initial degree of dyspnoea.

Supplemental oxygen during pulmonary rehabilitation in patients with COPD with exercise hypoxaemia

BACKGROUND Supplemental oxygen in patients with chronic obstructive pulmonary disease (COPD) and exercise hypoxaemia improves exercise capacity and dyspnoea. However, the benefit of oxygen during pulmonary rehabilitation in these patients is still unknown. METHODS Twenty five patients with stable COPD (mean (SD) forced expiratory volume in one second (FEV1) 0.76 (0.29) l and 30.0 (9.89)% predicted, arterial oxygen tension (Pao 2) 8.46 (1.22) kPa, arterial carbon dioxide tension (Paco 2) 6.32 (1.01) kPa) and significant arterial desaturation on exercise (82.0 (10.4)%) were entered onto a pulmonary rehabilitation programme. Patients were randomised to train whilst breathing oxygen (OT) (n = 13) or air (AT) (n = 12), both at 4 l/min. Assessments included exercise tolerance and associated dyspnoea using the shuttle walk test (SWT) and Borg dyspnoea score, health status, mood state, and performance during daily activities. RESULTS The OT group showed a significant reduction in dyspnoea after rehabilitation compared with the AT group (Borg mean difference –1.46 (95% CI –2.72 to –0.19)) but there were no differences in other outcome measures: SWT difference –23.6 m (95% CI –70.7 to 23.5), Chronic Respiratory Disease Questionnaire 3.67 (95% CI –7.70 to 15.1), Hospital Anxiety and Depression Scale 1.73 (95% CI –2.32 to 5.78), and London Chest Activity of Daily Living Scale –2.18 (95% CI –7.15 to 2.79). At baseline oxygen significantly improved SWT (mean difference 27.3 m (95% CI 14.7 to 39.8) and dyspnoea (–0.68 (95% CI –1.05 to –0.31)) compared with placebo air. CONCLUSIONS This study suggests that supplemental oxygen during training does little to enhance exercise tolerance although there is a small benefit in terms of dyspnoea. Patients with severe disabling dyspnoea may find symptomatic relief with supplemental oxygen.

Assessment and follow up of patients prescribed long term oxygen treatment.

BACKGROUND--Prescription and use of long term oxygen treatment were audited in a large group of patients after more than five years of use of the guidelines for its prescription. METHODS--Patients with a concentrator were interviewed at home with a structured questionnaire in three family health service authorities in East London. Stable oxygen saturation (SaO2) breathing air and oxygen, forced expiratory volume in one second (FEV1) and current and previous dated concentrator meter readings were recorded. A further questionnaire was sent to each patients general practitioner. Hospital case notes of patients who did not meet the criteria for long term oxygen treatment at reassessment were reviewed. RESULTS--A total of 176 patients were studied; 84% had chronic obstructive lung disease and 19% admitted to continued smoking; 140 patients had seen a respiratory physician but results of respiratory assessment were available to their general practitioner in fewer than 54 cases. FEV1 was < 1.5 1 in 158 patients but in 67 SaO2 was less than 91% breathing air, mainly in patients with chronic obstructive lung disease who had been inadequately assessed. Daily oxygen was prescribed for a median of 15 (range 4-24) hours and measured daily use was 15 (0-24) hours; 74% of patients used more than 12 hours. Only 35 patients had problems with oxygen treatment, but 29 had an undercorrected SaO2 of less than 92% when using their concentrator. CONCLUSIONS--Guidelines for prescription of long term oxygen treatment are largely followed and most patients complied with treatment. Increased communication about respiratory state is required between hospital doctors and general practitioners. Patients need regular reassessments to ensure that hypoxaemia is corrected and that oxygen is appropriately prescribed.

Does long-term oxygen therapy affect quality of life in patients with chronic obstructive pulmonary disease and severe hypoxaemia?

Long-term oxygen therapy (LTOT) improves survival in patients with hypoxaemic chronic obstructive pulmonary disease (COPD), but previous studies using general health measures have shown no effect on quality of life (QoL). In this study, the effect of LTOT on QoL was assessed using a disease-specific health measure, the St Georges Respiratory Questionnaire (SGRQ). Twenty three hypoxaemic COPD patients (15 females and 8 males) were studied before and after starting LTOT: median age 71 (range 47-82) yrs, mean (SD) forced expiratory volume in one second (FEV1) 0.75 (0.22) L, arterial oxygen tension (Pa,O2) 6.95 (0.75) kPa, arterial carbon dioxide tension (Pa,CO2) 6.52 (1.21) kPa. A control group comprised 18 COPD patients (6 females and 12 males) with less severe hypoxaemia: median age 72 (range 58-85) yrs, FEV1 0.94 (0.33) L, Pa,O2 8.17 (0.94) kPa, Pa,CO2 6.02 (0.75) kPa. QoL was measured at baseline, 2 weeks, 3 and 6 months. The LTOT group had higher SGRQ total scores than controls (p<0.05) at all visits, implying lower QoL. Repeated measures analysis of variance showed no effect of LTOT on QoL over 6 months (F=0.43, p=0.79). In this study we detected no change in quality of life using a disease-specific health measure in patients with severe chronic obstructive pulmonary disease using an oxygen concentrator to provide long-term oxygen therapy.

Renal Cell Carcinoma in Tuberous Sclerosis Complex

Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term “TSC-associated papillary RCC (PRCC).” The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC.

Anti-DNA autoreactivity in C4-deficient mice.

Mice lacking the classical complement component C4 (C4–/–) were evaluated for autoreactivity because classical complement deficiencies are major risk factors for human systemic lupus erythematosus (SLE). Naive, 6‐month‐old C4–/– mice have significantly more IgM anti‐double‐strand DNA antibodies than C4+/+ controls. By 9 months, IgG anti‐dsDNA antibodies are increased and this spontaneous autoreactivity is evident across a mixture of genetic backgrounds. C4+/– heterozygous mice also develop autoantibodies, reminiscent of the high incidence of partial C4 deficiency observed in human SLE. Kidneys of C4–/– mice have glomerular immune complexes, but progressive renal disease is not apparent in unmanipulated animals. Nonetheless, splenicB cells from C4–/– and not C4+/+ mice as young as 3 months can be triggered to secrete IgM anti‐dsDNA antibodies in vitro, before autoantibody titers are significantly elevated in vivo. These findings suggest that C4 normally helps prevent early stages of autoimmune disease and that C4 deficiency predisposes to abnormal regulation of autoreactive B cells.

Transient congenital hypoparathyroidism: Resolution and recurrence in chromosome 22q11 deletion

Transient congenital hypoparathyroidism (TCHP), with spontaneous resolution in infancy and subsequent recurrence in childhood, has not been associated with a specific cause. We report three patients with TCHP, initially with severe but transient neonatal hypocalcemia. During childhood, recurrence of hypoparathyroidism and recognition of phenotypic features suggested a diagnosis of velocardiofacial syndrome (VCFS). Features specific for the DiGeorge syndrome, with known clinical and genetic overlap with VCFS, were not present except for hypoparathyroidism. Genetic analysis confirmed chromosome 22q11 deletion in each patient. TCHP may be the earliest specific finding in 22q11 deletion/VCFS subgroup, with other diagnostic features emerging in later childhood. Infants with resolved TCHP need continued observation of parathyroid sufficiency, genetic analysis, and examination for anomalies associated with chromosome 22q11 deletion.

Nasal ventilation in acute exacerbations of chronic obstructive pulmonary disease: effect of ventilator mode on arterial blood gas tensions.

BACKGROUND--There are no controlled trials of the use of different modes of nasal intermittent positive pressure ventilation (NIPPV) in patients with exacerbations of chronic obstructive pulmonary disease (COPD). This study describes the effect on blood gas tensions of four different modes of nasal ventilation. METHODS--Twelve patients with acute exacerbations of COPD were studied (mean (SD) FEV1 0.59 (0.13) l, PaO2 (air) 5.10 (1.12) kPa, PaCO2 9.28 (1.97) kPa, pH 7.32 (0.03)). Each patient underwent four one-hour periods of nasal ventilation in randomised order: (a) inspiratory pressure support 18 cm H2O; (b) pressure support 18 cm H2O+positive end expiratory pressure (PEEP) 6 cm H2O (IPAP+EPAP); (c) continuous positive airway pressure (CPAP) 8 cm H2O; and (d) volume cycled NIPPV. Arterial blood samples were obtained before each period of ventilation and at one hour. RESULTS--Pressure support, CPAP, and volume cycled NIPPV all produced significant improvements in PaO2; there was no difference between these three modes. The change in PaO2 with IPAP+EPAP did not reach statistical significance. None of the modes produced significant changes in mean PaCO2; patients with higher baseline levels tended to show a rise in PaCO2 whereas those with lower baseline levels tended to show a fall. CONCLUSIONS--Although PaO2 improved in all patients there are differences in efficacy between the modes, while the changes in PaCO2 were variable. The addition of EPAP conferred no advantage in terms of blood gas tensions.

SAP-less chromatin triggers systemic lupus erythematosus.

Serum amyloid protein, highly conserved in both vertebrates and invertebrates, seems to exert a protective effect against autoimmune disease (pages 694–697).