Ventilatory responses to carbon dioxide in asthmatics with previous carbon dioxide retention during severe asthma

Ventilatory responses to carbon dioxide (Sco2) were measured in 15 asymptomatic asthmatic patients in whom CO2 retention had been documented during a previous attack of acute asthma. At the time when Sco2 was measured, the patients had normal or only mildly impaired ventilatory function (vital capacity (VC) 3,5 +/- 0,19 I, 98,7 +/- 4% of predicted (mean +/- SE); forced expiratory volume in 1 second (FEV1) 2,37 +/- 0,161, 83,8 +/- 5,2% of predicted; and FEV1/VC 68 +/- 2,5%). Fifteen control subjects without lung disease were also studied (VC 4,38 +/- 0,28 I, 103 +/- 2,6% of predicted; FEV1 3,76 +/- 0,23 I, 112 +/- 4,4% of predicted; FEV1/VC 86 +/- 7,8%). Sco2 in the patients (1,21 +/- 0,14 l/min/mmHg, range 0,62 - 2,81) was significantly different (P less than 0,001) from that in controls (2,13 +/- 0,17 l/min/mmHg, range 1,13 - 3,17). Sco2 in a subgroup of 5 patients with normal pulmonary function was also significantly different from that in controls. Correction for lung size (Sco2/VC) did not detract from the significance of the difference between patients and controls, suggesting that inherently low respiratory centre sensitivities to CO2 may have played a role in the development of hypercapnia during severe asthma in these patients.     

The risk of dying of prostate cancer in patients with clinically localized disease

From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.     

Demographic characteristics of patients with severe life threatening asthma: comparison with asthma deaths.

BACKGROUND--Studies of mortality from asthma have suggested that a very severe asthma attack identifies a group at greatly increased risk of subsequent death from the disease. This study compares the demographic characteristics of asthmatic patients who required management in an intensive care unit for a severe life threatening attack between 1981 and 1987 with a group who died of asthma between 1980 and 1986. The outcome of the group admitted to an intensive care unit is described. METHODS--The groups comprised all cases aged between 15 and 49 years arising from the Auckland Area Health Board (AAHB) population who required admission to an intensive care unit for asthma between 1981 and 1987 (n = 413) and all deaths from asthma in those aged 15 to 49 years arising from the New Zealand population between 1980 and 1986 (n = 466). Details of age, sex, and information on the day and month of the attack were collected. For the group requiring admission to an intensive care unit, outcome in terms of mortality and readmission to intensive care was determined. RESULTS--The age distributions of the two groups were dissimilar, with the severe life threatening attack group having an excess of asthmatic patients under 30 years old. The distribution of events by calendar month was uniform in both groups, but there was an unexpected increase in frequency of attacks on Sundays in both groups. Over the study period, mortality fell from 5.3 per 100,000 to 3.5 per 100,000 but the admission rate to intensive care increased from 10.8 per 100,000 to 17.9 per 100,000. At least 24% of asthma deaths occurring in the AAHB region during the study period had previously experienced a severe life threatening attack. CONCLUSIONS--The similarities between the groups suggest that asthmatic patients who experience severe life threatening attacks are likely to come from the same subgroup of the asthma population as those who die. The group who experience severe life threatening attacks are at high risk of subsequent morbidity and mortality and further studies may produce information relevant to reducing mortality from asthma.     

Effect of nitric oxide predilution on inhaled nitrogen dioxide concentrations

We examined the possibility that predilution of a concentrated nitric oxide (NO) source with nitrogen, before contact with oxygen, can reduce the inspired nitrogen dioxide (NO2) concentration during administration of nitric oxide. A Manley Blease and a Siemens Servo 900 C ventilator delivered 10, 20, 40, 60 and 80 parts per million (ppm) NO using an NO source of 1000, 400 and 200 ppm. With the Manley Blease system, predilution from 1000 to 200 ppm NO reduced the inhaled NO2 concentration from 0.14 to 0.05 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.20 to 1.00 ppm (p < 0.01) at 40 ppm inhaled NO. With the Siemens Servo 900 C ventilator, inspiratory NO2 concentrations decreased from 0.21 to 0.11 ppm (p < 0.01) at 10 ppm inhaled NO, and from 1.49 to 1.16 ppm (p < 0.01) at 40 ppm NO. Predilution from 1000 to 400 ppm NO reduced the inspired NO2 concentrations by < 3% using either ventilator when the inspirated NO concentration was 80 ppm. Predilution of NO with nitrogen significantly reduced the inspired NO2 concentrations for nitric oxide concentrations between 10 and 40 ppm, but offered no clinically relevant advantage at higher NO concentrations.     

Effect of leukotriene receptor antagonist therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials

BACKGROUND: Asthma exacerbations contribute substantially to morbidity, and their reduction is an important therapeutic objective. In this integrated analysis the risk of asthma exacerbations was assessed during treatment with the leukotriene receptor antagonist zafirlukast. METHODS: Data were collected from all five double blind, multicentre, randomised, placebo controlled, 13 week trials of zafirlukast 20 mg twice daily performed in steroid-naive patients with mild to moderate asthma. Exacerbation data were collected prospectively during monitoring of adverse events and concomitant medication use. Pooled data were used to assess the relative risk of asthma exacerbations using three definitions: worsening of asthma leading to withdrawal from the study; requirement for additional anti-asthma therapy (excluding increased short acting beta(2) agonist use); and requirement for oral corticosteroid therapy. RESULTS: The proportion of patients with an asthma exacerbation leading to withdrawal was consistently lower in the group treated with zafirlukast 20 mg twice daily than in the placebo group. Overall, the risk of an asthma exacerbation requiring withdrawal from zafirlukast therapy was approximately half that of placebo (odds ratio 0.45; 95% CI 0.26 to 0.76; p = 0.003). Similar results were observed for exacerbations requiring additional control medication (odds ratio = 0.47; 95% CI 0.30 to 0.74; p = 0.001) and oral corticosteroid rescue (odds ratio = 0.53; 95% CI 0.32 to 0.86; p = 0.010). CONCLUSIONS: Zafirlukast in a dose of 20 mg twice daily reduces the risk of asthma exacerbations and the need for additional anti-asthma therapies, fulfilling an important goal of control medication in patients with mild to moderate asthma.     

Personal exposure to nitrogen dioxide and risk of airflow obstruction in asthmatic children with upper respiratory infection

BACKGROUND: Several studies have linked air pollution by nitrogen dioxide (NO(2)) with increased hospital admissions for asthma in children. Exacerbations of asthma in children are often precipitated by upper respiratory infections. It is therefore possible that NO(2) increases the risk of airways obstruction when asthmatic children develop upper respiratory infections. METHODS: To test this hypothesis a sample of 114 asthmatic children aged 7-12 years were followed for a total of up to 13 months. Probable upper respiratory infections were identified by consensus review of daily symptom diaries, and episodes of airways obstruction from serial records of peak expiratory flow (PEF). Personal exposures to NO(2) were measured with Palmes tubes that were changed weekly. Generalised estimating equations were used to assess the relative risk (RR) of an asthmatic exacerbation starting within seven days of an upper respiratory infection according to estimated NO(2) exposure during the one week period from two days before to four days after the onset of the infection. RESULTS: The children were followed for an average of 34 weeks during which 318 upper respiratory infections and 224 episodes of reduced PEF were diagnosed. PEF episodes were much more likely to occur in the seven days following the onset of an upper respiratory infection than at other times. Estimated exposures to NO(2) at the time of infections were generally low (geometric mean 10.6 microg/m(3)). Compared with exposures of < or = 8 microg/m(3), exposures of >28 microg/m(3) were associated with a RR of 1.9 (95% confidence interval 1.1 to 3.4) for the development of an asthmatic episode within seven days of an infection. CONCLUSIONS: The findings give some support to the hypothesis that NO(2) increases the risk of asthmatic exacerbations following respiratory infections, even at relatively low levels of exposure. Further studies in populations with higher exposures would be useful.     

Effect of aerosol fenoterol on the severity of bronchial hyperreactivity in patients with asthma

Beta adrenergic agents given by aerosol decrease the responsiveness of the airways to histamine and methacholine in subjects with asthma, causing a shift of the dose response curve to the right. To find out whether the shift is related to the dose of beta adrenergic agent given and to determine the duration of the reduced responsiveness, eight subjects with asthma were given histamine inhalation tests after inhaled saline and after increasing doses of inhaled fenoterol on different days. The histamine inhalation tests were repeated at hourly intervals for five hours after a selected dose of fenoterol. Fenoterol caused a dose related shift to the right of the histamine dose response curve in each subject and in some the dose response relationship reached the "non-symptomatic range." The shift in the dose response curve was short lived and had returned towards the control position within three hours in all subjects. There was no change in shape of the curves at the time of maximal shift. The results show that inhaled fenoterol greatly reduces the airway responsiveness to histamine, but up to 400 micrograms of fenoterol every four to five hours may be needed to keep the responsiveness of the airways in the non-symptomatic range.     

Effect of varicocelectomy on patients with unobstructive azoospermia and severe oligospermia

OBJECTIVES

To assess the treatment outcome and benefits after varicocelectomy in men with unobstructive azoospermia (UOA) and severe oligospermia (SO).

PATIENTS AND METHODS

The records were retrospectively evaluated for six patients with UOA and 54 with SO who had microsurgical inguinal varicocele ligation (mean age 33.3 years, sd 5.3). Fifty‐one (85%) had a unilateral left‐sided procedure (five of six with UOA, 46 of 54 with SO), and nine (15%) had a bilateral procedure.

RESULTS

After ligation, spermatogenesis was induced in two of the six men with UOA; the mean (sd ) sperm concentration increased from 2.3 (1.6) to 9.2 (12.6) million/mL (P < 0.001), but the sperm motility did not change significantly. Four (7%) of the 54 men with SO achieved paternity, with unassisted pregnancies.

CONCLUSIONS

Varicocelectomy resulted in the induction or enhancement of spermatogenesis for several men with UOA or SO; it seems to be a reasonable option in selected patients with UOA or SO.     

Comparison of oral prednisolone and intramuscular depot triamcinolone in patients with severe chronic asthma.

In a double blind crossover study oral prednisolone was compared with intramuscular depot triamcinolone in the treatment of 20 patients with severe chronic asthma. A short term study comparing each treatment over four weeks showed only minor differences in therapeutic efficacy, but at the end of 24 week periods on each of the two treatments triamcinolone was significantly more effective than prednisolone in terms of forced expiratory volume in one second and forced vital capacity. Better control of asthma was accompanied by a significant fall in weight and some evidence of reduced adrenal suppression (improved cortisol response following a short tetracosactrin test). Side effects, including menstrual irregularities, muscle pain, and hirsuitism, were, however, more common during treatment with triamcinolone.     

The effects of laparoscopic Nissen fundoplication on patients with severe gastroesophageal reflux disease and steroid-dependent asthma

BackgroundAn association between severe reactive airway disease (RAD) and gastroesophageal reflux disease (GERD) in children has been previously noted, but the relationship has not been well characterized. This study reports our experience with laparoscopic Nissen fundoplication and its effect on the pulmonary status of children with severe steroid-dependent RAD.MethodsBetween January 1993 and June 2011, 235 patients with severe steroid-dependent RAD and medically refractory GERD underwent laparoscopic Nissen fundoplication. Clinical response, ability to wean oral and inhaled steroids, and changes in pulmonary function testing were tracked during the postoperative period.ResultsOf 235 patients, 215 (91%) noted significant subjective improvement in their respiratory symptoms by the first postoperative visit at 2 weeks. Eighty percent was successfully weaned off their oral steroids within the first 2 postoperative months. Ninety-five percent reported a decrease in their inhaler use. Twenty-four percent of patients studied had a documented increase in their forced expiratory volume in the initial postoperative period. There were no intraoperative complications and no postoperative respiratory tract infections.ConclusionChildren with steroid-dependent RAD and documented GERD refractory to medical management show improvement in their respiratory status after laparoscopic Nissen fundoplication. Many can be weaned off of their oral and inhaled steroids postoperatively.     

Effectiveness of nebulised salbutamol administered in ambulances to patients with severe acute asthma.

BACKGROUND--Nebulised salbutamol can now be administered by ambulance personnel to patients with severe acute asthma en route to hospital. This treatment, however, is not yet available in all ambulances. The safety and effectiveness of allowing ambulance crews to initiate treatment with nebulised salbutamol has been assessed in patients with acute severe asthma. METHODS--After a basic training course in the assessment of asthma and the use of a nebuliser, ambulance crews initiated treatment with nebulised salbutamol in asthmatic patients under the age of 40 years. Airflow obstruction was measured before and after treatment with a peak flow meter. A subjective assessment of any change in the patient's condition was also made. RESULTS--Nebuliser treatment was associated with a significant increase in peak flow in almost 80% of patients who had recordable values before and after treatment. The mean percentage increase in peak flow was 56.5%. Subjective assessments correlated well with peak flow measurements. No unwanted side effects were recorded. CONCLUSIONS--Nebulised salbutamol is an effective and safe treatment for acute asthma when administered by ambulance personnel after a short training course.     

Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma.

BACKGROUND--Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS--Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS--Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS--Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy.     

Early risk factors for sepsis in patients with severe blunt trauma

We studied 43 patients with blunt trauma (injury severity score, > or =25), age >14 years and length of the intensive care unit (ICU) stay >48 h in order to estimate the frequency of sepsis and to identify early risk factors related to its development. Clinical data were collected during the first 24 h and several inflammatory mediators were determined from serum samples of the first 2 days after injury.Twenty-one patients (48.8%) met sepsis criteria during their ICU stay, 9 (20.9%) fulfilled only criteria for sepsis; 6 (13.9%) fulfilled criteria for severe sepsis and another 6 (13.9%) criteria for septic shock.An APACHE II score > or =14, the presence of hypovolemic shock, the need for three or more units of blood to be transfused and the administration of a total volume of fluids > or =10 l were all factors associated significantly with the development of sepsis. In the multivariant analysis, the need for a total volume of fluids > or =10 l was the only independent risk factor (adjusted odds ratio=10.49, 95% CI, 2.34-47.02; P=0.002). No significant differences were documented in relation to the behaviour of the serum markers.     

Effect of nitrogen on carbon dioxide elimination during continuous flow apneic ventilation in dogs

Continuous endobronchial insufflation of air in paralyzed animals (continuous flow apneic ventilation - CFAV) has been shown to maintain adequate oxygenation and carbon dioxide removal. CFAV in patients using oxygen resulted in adequate oxygenation but a mean rise in PaCO2 of 0.6 mmHg/min (0.08 kPa/min). This experiment compared carbon dioxide removal in dogs with air and oxygen. Ten dogs were anesthetized and paralyzed, and CFAV was used for 1 h with either air or oxygen in a randomized fashion. Adequate oxygenation was obtained with air and oxygen. Normal PaCO2 levels were obtained with air; however, in the animals where oxygen was used, PaCO2 levels rose to a mean of 6.45 +/- s.e. mean 0.4 kPa (48.5 +/- s.e.mean 3.2 mmHg).     

Urban-rural location and the risk of dying in a pedestrian-vehicle collision

Statewide data from two sources were used to compare the pedestrian-vehicle collision injury and fatality rates for urban and rural areas of Washington State from 1981 through 1983. Although the rates of pedestrian injuries are higher in urban areas, the pedestrian fatality rate in rural areas is higher for nearly all age groups, and at all posted speeds. Multiple logistic regression was carried out to measure the risk of dying once involved in a pedestrian-vehicle collision in rural areas compared to the risk for urban areas. This relative risk was seen to be elevated (RR = 2.3; 95% CI = 2.0-2.6) even after controlling for the effects of age and sex of the pedestrian, and posted speed of the vehicle. When explored further it was seen that a larger proportion of fatalities died out of the hospital and within the first hour after injury in rural areas than in urban areas. It is possible that Emergency Medical Services care is less rapidly available and that accessibility to trauma centers is more limited in rural areas.