Cystatin C does not detect acute changes in glomerular filtration rate in early diabetic nephropathy

BACKGROUND: The measurement of renal functional reserve (acute change in glomerular filtration rate [GFR] after protein load) allows the detection of sub-clinical renal dysfunction and has prognostic implications in diabetes. Our aim was to test cystatin C as an index of GFR and renal functional reserve. METHODS: GFR was measured by C(Sinistrin) at baseline and after protein load in 28 diabetic patients with serum creatinine <1.2 mg/dL. The C(Sinistrin) was compared with cystatin C, serum creatinine, creatinine clearance, and Cockcroft-Gault formula. RESULTS: Baseline C(Sinistrin) ranged from 67-172 mL/min. Regression analysis showed an overall low relationship between C(Sinistrin) and the indirect markers of GFR. The highest correlation with C(Sinistrin) was obtained for cystatin C clearance (R(2) = 0.58, r = 0.76, p < 0.001), the 1/serum cystatin C (R(2) = 0.58, r = 0.76, p < 0.001), and serum cystatin C (R(2) = 0.52, r = 0.72, p < 0.001). Renal functional reserve was preserved in 6 of 28 patients. There was no significant change in cystatin C in response to protein load. CONCLUSION: Wide variation in baseline GFR emphasizes the need for the early detection of renal dysfunction. Cystatin C correlated best with C(Sinistrin) at baseline, but did not detect renal functional reserve.     

Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD. METHODS: Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order. RESULTS: FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4). CONCLUSION: Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.


     

Outcome of domiciliary nasal intermittent positive pressure ventilation in restrictive and obstructive disorders.

BACKGROUND--Nasal intermittent positive pressure ventilation (NIPPV) is a new technique which has rapidly supplanted other non-invasive methods of ventilation over the last 5-10 years. Data on its effectiveness are limited. METHODS--The outcome of long term domiciliary NIPPV has been analysed in 180 patients with hypercapnic respiratory failure predominantly due to chest wall restriction, neuromuscular disorders, or chronic obstructive lung disease. One hundred and thirty eight patients were started on NIPPV electively, and 42 following an acute hypercapnic exacerbation. Outcome measures were survival (five year probability of continuing NIPPV), pulmonary function, and health status. A crossover study from negative pressure ventilation to NIPPV was carried out in a subgroup of patients. RESULTS--Five year acturial probability of continuing NIPPV for individuals with early onset scoliosis (n = 47), previous poliomyelitis (n = 30), following tuberculous lung disease (n = 20), general neuromuscular disorders (n = 29), and chronic obstructive pulmonary disease (n = 33) was 79% (95% CI 66 to 92), 100%, 94% (95% CI 83 to 100), 81% (95% CI 61 to 100), 43% (95% CI 6 to 80), respectively. Most of the patients with bronchiectasis died within two years. One year after starting NIPPV electively the mean (SD) PaO2 compared with the pretreatment value was +1.8 (1.9) kPa, mean PaCO2 -1.4 (1.3) kPa in patients with extrapulmonary restrictive disorders, and PaO2 +0.8 (1.0) kPa, PaCO2 -0.9 (0.8) kPa in patients with obstructive lung disease. Arterial blood gas tensions improved in patients transferred from negative pressure ventilation to NIPPV. Health status was ranked highest in patients with early onset scoliosis, previous poliomyelitis, and following tuberculous lung disease. In the group as a whole health perception was comparable to outpatients with other chronic disorders. CONCLUSIONS--The long term outcome of domiciliary NIPPV in patients with chronic respiratory failure due to scoliosis, previous poliomyelitis, and chest wall and pulmonary disease secondary to tuberculosis is encouraging. The results of NIPPV in patients with COPD and progressive neuromuscular disorders show benefit in some subgroups. The outcome in end stage bronchiectasis is poor.     

Renal response to a protein load persists during long-term follow-up of children after renal transplantation

BACKGROUND: Kidney donors and transplant recipients may be at risk of complications from glomerular hyperfiltration of the single kidney. It has been assumed that tests of the existence of renal functional reserve [delta glomerular filtration rate (deltaGFR), delta effective renal plasma flow (deltaERPF)] can be used to demonstrate hyperfiltration. It would therefore be of interest to evaluate the response of the kidney graft to a protein load. i.e., testing the renal reserve and to find out whether a reduction in baseline GFR is preceded by a loss of deltaGFR. METHODS: We repeatedly studied the change in GFR and renal plasma flow (ERPF) after an oral protein load in 30 children after renal transplantation (Tx). Follow-up time was 1.0-8.0 years. Renal function was evaluated with the clearances of inulin and para-aminohippuric acid (PAH). Seven recipient/donor pairs were examined twice (median 0.3 and 4 years, after Tx). RESULTS: The baseline GFR and ERPF remained stable throughout the follow-up and the increase after stimulation (deltaGFR and deltaERPF) did not change in the whole group of Tx children over the years. However, a reduction in the baseline GFR from the first to the last investigation occurred in 23 of 30 children. In the 23 patients whose baseline GFR decreased, deltaGFR was still preserved. In the recipient/donor pairs, the baseline GFR and ERPF were the same, but on the second investigation, donors showed higher deltaGFR. CONCLUSION: Despite fairly low baseline GFR and ERPF values in the Tx children, no change occurs in the capacity to increase GFR and ERPF after a protein load during follow-up, which suggests that they are not maximally hyperfiltrating.     

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.     

Cyclosporin A abolishes renal reserve capacity.

Renal functional reserve (RFR) was investigated in a group of renal transplant recipients taking cyclosporin A (CyA) immunosuppressive therapy. Nine patients received a 93 g oral protein load containing 5983 mg of glycine. GFR and ERPF were measured using isotope infusions of 51Cr EDTA and 125I OIH, respectively, before and for 3 h after the meal. Patients studied demonstrated a wide range of baseline GFRs (20.9-89.5 mL/min, mean 50.09 mL/min). However, few patients demonstrated an individual RFR, regardless of original level of function. Overall, no significant change in either GFR or ERPF was demonstrated after the protein stimulus. CyA is known to alter intrarenal prostanoid synthesis in favor of vasoconstriction and RFR is thought to be mediated by prostanoids. Therefore a mechanism for the absence of RFR in patients receiving CyA therapy is suggested.     

One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: implications for the provision of non-invasive ventilation and oxygen administration

BACKGROUND: Non-invasive ventilation (NIV) reduces mortality and intubation rates in patients with chronic obstructive pulmonary disease (COPD) admitted to hospital with respiratory acidosis. This study aimed to determine the prevalence of respiratory acidosis in patients admitted with COPD, to draw inferences about oxygen therapy, and to determine the need for NIV services for acute COPD in typical UK hospitals. METHODS: This one year prospective prevalence study identified patients with COPD aged 45-79 years inclusive who were admitted to Leeds General Infirmary, St James's University, and Killingbeck Hospitals, Leeds between 1 March 1997 and 28 February 1998. The prevalence of respiratory acidosis and the relationship with oxygenation are described. Other outcomes included intensive care use and in hospital mortality. From this data population prevalence estimates were determined for respiratory acidosis, from which the need for NIV in a typical district general hospital was modelled. RESULTS: 983 patients were admitted, 11 of whom required immediate intubation. 20% of the remaining 972 had a respiratory acidosis. Acidosis was associated with subsequent admission to the intensive care unit (ICU): pH<7.25, OR 6.10 (95% confidence interval (CI) 1.19 to 31.11); pH 7.25-7.30, OR 8.73 (95% CI 2.11 to 36.06). pH was inversely correlated with arterial oxygen tension (PaO(2)) in the 47% of patients who were hypercapnic, with a PaO(2) of >10 kPa being associated with acidosis in most hypercapnic patients. 80% remained acidotic after initial treatment, giving an age/sex specific prevalence for England and Wales of 75 (95% CI 61 to 90)/100 000/year for men aged 45-79 years and 57 (95% CI 46 to 69)/100 000/year for women. Modelling the need for NIV for all COPD patients indicates that a typical UK hospital will admit 90 patients per year with acidosis of which 72 will require NIV. CONCLUSIONS: In patients with acute COPD the PaO(2) should be maintained at 7.3-10 kPa (SaO(2) 85-92%) to avoid the dangers of hypoxia and acidosis. If all COPD patients with a respiratory acidosis (pH<7.35) after initial treatment are offered NIV, a typical UK hospital will treat 72 patients per year.     

Effect of adenosine infusion on oxygen induced carbon dioxide retention in severe chronic obstructive pulmonary disease.

BACKGROUND: In normal subjects intravenous adenosine infusion has been shown to stimulate ventilation with a consequent fall in arterial partial pressure of carbon dioxide (Paco2), probably by an action on the carotid bodies. The objective of this study was to determine whether the increase in Paco2 seen when patients with ventilatory failure secondary to chronic obstructive pulmonary disease (COPD) are given a high concentration of oxygen to breathe might be ameliorated by an intravenous infusion of adenosine. METHODS: Eight subjects with chronic stable ventilatory failure secondary to COPD were studied. Their mean (SE) forced expiratory volume in one second (FEV1) was 0.63 (0.12) 1 with forced vital capacity (FVC) of 1.63 (0.21) 1. They received continuous intravenous infusions of saline and adenosine in random order, double blind. The infusions were administered for two minutes at 20 micrograms/kg/min, increasing in increments of 20 micrograms/kg/min every two minutes to a maximum infusion rate of 80 micrograms/kg/min adenosine (or an equivalent saline infusion rate), or until side effects supervened. The infusions were continued at that rate for five minutes, after which the fractional inspired oxygen (FIO2) was raised to 0.50 during a further 20 minutes of the infusion at that rate. Haemoglobin oxygen saturation (SaO2) and transcutaneous PCO2 (PtcCO2) were monitored throughout the procedure. Spirometric tests were performed before and after each infusion. RESULTS: Adenosine infusion was accompanied by a fall in PtcCO2 from a mean (SE) of 7.29 (0.42) kPa to 6.95 (0.48) kPa: mean difference -0.34 (95% confidence interval, -0.56 to -0.11) kPa. During saline infusion oxygen administration resulted in an increase in transcutaneous PtcCO2 from 7.35 (0.34) kPa to 7.88 (0.28) kPa: mean difference 0.53 (95% CI 0.20 to 0.85) kPa. PtcCO2 did not rise above baseline levels when oxygen was administered during the adenosine infusion. A small fall in FVC was seen following adenosine infusion. CONCLUSIONS: The increase in PtcCO2 seen when patients with stable ventilatory failure secondary to severe COPD are given a high concentration of oxygen to breathe is counteracted by a continuous intravenous infusion of adenosine.     

PI SZ phenotype in chronic obstructive pulmonary disease

BACKGROUND: A study was undertaken to clarify whether the PI SZ phenotype of the protease inhibitor system predisposes to chronic obstructive pulmonary disease (COPD). METHODS: The prevalence of PI Z and PI SZ deficient phenotypes was investigated in a population of 702 patients with COPD followed up at the Chest Unit of a tertiary hospital and in 15400 newborn infants from the same geographical area. Individuals with deficiency were detected by screening of dried blood spots on filter paper using a comparative electro-immunodiffusion technique for alpha 1-antitrypsin and transferrin. The serum phenotype was confirmed by means of isoelectrofocusing on polyacrylamide gel. RESULTS: Of the 702 blood samples from patients with COPD, six PI Z subjects (0.85%) and one PI SZ (0.14%) were detected. Of the 15400 samples from neonates, the number of PI Z subjects was eight (0.052%) and that of PI SZ was 24 (0.156%). The difference between the two groups was significant for PI Z but not for PI SZ. CONCLUSIONS: The data do not indicate an increased risk for development of COPD associated with the PI SZ phenotype but confirm the predisposition of PI Z individuals for the development of COPD.


     

The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients

Hemodynamic changes and plasma catecholamine levels after naloxone administration were studied in seventeen postoperative patients who received nitrous oxide, oxygen, and fentanyl anesthesia combined with epidural block. Group I consisted of ten postoperative hypercapnic (Pa_{CO 2} = 55.2 ± 2.4 torr) and group II seven postoperative normocapnic patients (Pa_{CO 2} = 38.4 ± 2.1 torr), respectively. In group I, naloxone reversal resulted in significant increases in heart rate (13.5%), mean arterial pressure (46.6%), systemic vascular resistance (32.1%), and rate pressure product (68.8%), whereas mean pulmonary artery pressure and pulmonary vascular resistance were significantly decreased. No significant hemodynamic changes after naloxone administration were observed in group II. There were no significant differences in arterial norepinephrine and epinephrine levels either before or after naloxone administration in the both groups. This study indicates that the postoperative hypercapnia elicits the cardiovascular stimulation after fentanyl reversal by naloxone.(Kishikawa K, Namiki A, Iwasaki H: The cardiovascular effects of naloxone administration after fentanyl anesthesia in hypercapnic patients. J Anesth 3: 48–53, 1989)     

Physiological effects and optimisation of nasal assist-control ventilation for patients with chronic obstructive pulmonary disease in respiratory failure

BACKGROUND: A study was undertaken to investigate the effects of non- invasive assist-control ventilation (ACV) by nasal mask on respiratory physiological parameters and comfort in acute on chronic respiratory failure (ACRF). METHODS: Fifteen patients with chronic obstructive pulmonary disease (COPD) were prospectively and randomly assigned to two non-invasive ventilation (NIV) sequences in spontaneous breathing (SB) and ACV mode. ACV settings were always optimised and therefore subsequently adjusted according to patient's tolerance and air leaks. RESULTS: ACV significantly decreased all the total inspiratory work of breathing (WOBinsp) parameters, pressure time product, and oesophageal pressure variation in comparison with SB mode. The ACV mode also resulted in a significant reduction in surface diaphragmatic electromyographic activity to 36% of the control values and significantly improved the breathing pattern. SB did not change the arterial blood gas tensions from baseline values whereas ACV significantly improved both the PaO2 from a mean (SD) of 8.45 (2.95) kPa to 13.31 (2.15) kPa, PaCO2 from 9.52 (1.61) kPa to 7.39 (1.39) kPa, and the pH from 7.32 (0.03) to 7.40 (0.07). The respiratory comfort was significantly lower with ACV than with SB. CONCLUSIONS: This study shows that the clinical benefit of non-invasive ACV in the management of ACRF in patients with COPD results in a reduced inspiratory muscle activity providing an improvement in breathing pattern and gas exchange. Despite respiratory discomfort, the muscle rest provided appears sufficient when ACV settings are optimised.


     

Renal functional reserve in transplanted and native single kidneys of children and adults

Renal functional reserve (RFR) after an oral protein load was evaluated in 36 cyclosporine-treated children following kidney transplantation (Tx), in 15 kidney donors (Don), and in 15 children with single kidneys (Nx/Ag). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by clearances of inulin (and creatinine) and para-aminohippurate during water diuresis. Baseline and stimulated GFR and ERPF were determined and RFR was calculated as the difference between stimulated and baseline values. Baseline GFR and ERPF in Tx were lower than in Don and Nx/Ag. Both GFR and ERPF increased significantly in all groups from baseline to stimulated values. RFR GFR was 23%±3%, 20%±3% and 15%±3% in Tx, Don, and Nx/Ag and RFR ERPF 35%±4% in Tx, which was significantly higher than 20%±4% and 15%±3% in the two other groups respectively. Stimulated GFR and ERPF in Tx correlated with kidney length. No differences were seen in recipient-donor pairs, except for higher fractional increases of ERPF in recipients. There was no correlation between RFR measured by clearance of creatinine and clearance of inulin. In conclusion, cyclosporine-treated children following renal Tx were found to have a renal reserve capacity. Received September 19, 1995; received in revised form September 16, 1996; accepted October 1, 1996     

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 (FEV(1)) 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.     

Glomerular function and renal functional reserve

Protein intake has been shown to raise glomerular filtration rate (GFR). The difference between peak and baseline GFR following acute protein load indicates renal functional reserve (RFR). In this paper, we review 1) normal glomerular function and its regulating factors, 2) the concept of RFR and the mechanism by which the acute protein load induces hyperfiltration response in healthy subjects and 3) the RFR in patients with renal disease.     

Cough threshold in patients with chronic obstructive pulmonary disease

BACKGROUND: Cough is an important symptom of patients with chronic obstructive pulmonary disease (COPD). The cough threshold to citric acid and capsaicin in patients with COPD and in normal volunteers was measured, as well as bronchial hyperresponsiveness to methacholine. METHODS: Nineteen patients with COPD and 22 controls were recruited. Subjects underwent a methacholine bronchoprovocation test and a cough challenge to citric acid and capsaicin. RESULTS: The log citric acid cough threshold D2 (concentration causing two coughs) was significantly lower in patients with COPD (mean 2.17 versus 2.56, mean difference (95% CI) 0.39 (0.04 to 0.74), p = 0.02) but not for capsaicin cough D2 (0.66 versus 0.8, p = 0.41). Sixteen patients with COPD had bronchial hyperresponsiveness which was correlated with baseline FEV1 (r = 0.6, p = 0.01, 95% CI 0.15 to 0.84). CONCLUSIONS: Patients with COPD have a lower cough threshold to citric acid, possibly due to a differential effect of cigarette smoke on citric acid sensitive cough receptors.     

Proportional assist ventilation as an aid to exercise training in severe chronic obstructive pulmonary disease

BACKGROUND: The effects of providing ventilatory assistance to patients with severe chronic obstructive pulmonary disease (COPD) during a high intensity outpatient cycle exercise programme were examined. METHODS: Nineteen patients (17 men) with severe COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 27 (7)% predicted) underwent a 6 week supervised outpatient cycle exercise programme. Ten patients were randomised to exercise with ventilatory assistance using proportional assist ventilation (PAV) and nine (two women) to exercise unaided. Before and after training patients performed a maximal symptom limited incremental cycle test to determine peak work rate (Wpeak) followed by a constant work rate (CWR) test at 70% of Wpeak achieved in the baseline incremental test. Minute ventilation (VE), heart rate, and arterialised venous plasma lactate concentration [La(+)] were measured before and after each test. RESULTS: Mean training intensity (Wt/Wpeak) at 6 weeks was 15.2% (95% CI 3.2 to 27.1) higher in the group that used ventilatory assistance (p=0.016). Peak work rate after training was 18.4% (95% CI 6.4 to 30.5) higher (p=0.005) in the assisted group (p=0.09). [La(+)] at an identical workload after training was reduced by 30% (95% CI 16 to 44) in the assisted group (p=0.002 compared with baseline) and by 11% (95% CI -7 to 31) (p=0.08 compared with baseline) in the unassisted group (mean difference 18.4% (95% CI 3.3 to 40), p=0.09). A significant inverse relationship was found between reduction in plasma lactate concentration (DeltaL) at an equivalent workload after training during the CWR test and Wt/Wpeak achieved during the last week of training (r=-0.7, p=0.0006). CONCLUSIONS: PAV enables a higher intensity of training in patients with severe COPD, leading to greater improvements in maximum exercise capacity with evidence of true physiological adaptation.     

Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia

BACKGROUND: Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV. METHODS: Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria. RESULTS: Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months. CONCLUSION: Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.     

Randomised controlled trial of inhaled corticosteroids in patients with chronic obstructive pulmonary disease

BACKGROUND—Inhaled corticosteroids are known to bebeneficial for patients with asthma, but their role in treatingpatients with stable chronic obstructive pulmonary disease (COPD)remains controversial. A study was undertaken to determine whetherinhaled corticosteroids are of functional benefit in patients who didnot show improvement with a trial of oral corticosteroids.
METHODS—In phase I patients with stable COPD weregiven a two week course of oral placebo followed by two weeks ofprednisone 40 mg per day in a single blind manner to distinguishbetween responders and non-responders to oral corticosteroids. In phaseII a double blind, randomised, parallel group trial of inhaledbudesonide 1600 µg per day versus placebo was carried out in 79 non-responders to oral corticosteroids. The primary outcome measure wasforced expiratory volume in one second (FEV₁), andsecondary outcome measures were exercise capacity, dyspnoea withexertion, quality of life, peak expiration flow rate, and respiratory symptoms.
RESULTS—Randomisation allocated 39 subjects toinhaled corticosteroids and 40 to placebo. There was no difference inthe change in FEV₁ from baseline between the treatment andplacebo groups; mean difference -12 ml (95% CI -88 to 63) at threemonths and -4 ml (95% CI -95 to 87) at six months. The proportionof patients with a 15% or greater improvement was no higher amongthose receiving inhaled corticosteroids than in the placebo group atany of the follow up visits. Changes in secondary outcomes were also no different.
CONCLUSIONS—Inhaledcorticosteroids,even at high doses, were of no physiological or functional benefit inthese patients with advanced COPD.

     

Inhaled corticosteroids reduce neutrophilic bronchial inflammation in patients with chronic obstructive pulmonary disease

BACKGROUND—Airwaysinflammation is a feature of chronic obstructive pulmonary disease(COPD), but the role of corticosteroids in the management ofclinically stable patients has yet to be established. A randomisedcontrolled study was carried out to investigate the effect of high doseinhaled beclomethasone dipropionate (BDP) administered for two monthsto patients with stable, smoking related COPD. Sputum induction wasused to evaluate bronchial inflammation response.
METHODS—34 patients(20 men and 14 women) were examined on three separate occasions. At theinitial clinical assessment (visit 0), spirometry and blood gasanalysis were performed. On visit 1 (within one week of visit 0) sputuminduction was performed and each patient was randomised to receiveeither BDP 500 µg three times daily (treated group) or nothing(control group). After two months (visit 2), all patients underwentrepeat clinical assessment, spirometry, and sputum induction.
RESULTS—There were nodifferences in sputum cell counts between the groups at baseline. Aftertwo months of treatment, induced sputum samples from patients in thetreated group showed a reduction in both neutrophils (−27%) andtotal cells (−42%) with respect to baseline, while the control groupdid not (neutrophils +9%, total cells +7%). Macrophages increased inthe treated group but not in the control group. The mean final value ofsputum neutrophils was 52% in the treated group and 73.3% in thecontrol group (95% confidence interval (CI) −27.2 to −15.4). Themean final value of sputum macrophages was 35.8% in treated group and19.3% in control group (95% CI 10.3 to 22.8). The differences betweenthe treated and control groups for neutrophils (−21.3%), macrophages (+16.5%), and total cells (−65%) were significant. Spirometry andblood gas data did not change from baseline in either patient group.
CONCLUSIONS—A twomonth course of treatment with high dose inhaled BDP reducessignificantly neutrophil cell counts in patients with clinically stable, smoking related COPD. Further studies on the effectiveness ofinhaled steroids in COPD are needed to confirm the clinical importanceof this observation.