Exhaled nitric oxide in cystic fibrosis patients with allergic bronchopulmonary aspergillosis.

Exhaled nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO in CF patients at high risk of developing ABPA and patients at low risk. We studied nine patients at high risk of developing ABPA and 36 at low risk. The two groups were similar in age and spirometry. All patients in the high-risk group were taking oral or inhaled glucocorticoids, compared to 56% in the low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6 to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids, the exhaled NO levels were significantly lower in patients with a high risk of developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number of patients who were on inhaled, but not oral glucocorticoids was too small to analyse usefully. Exhaled NO levels were lower in CF patients with a high risk of developing ABPA and on glucocorticoids. This may be because oral glucocorticoids exert a greater effect on exhaled NO than inhaled glucocorticoids. Alternatively, inducible nitric oxide synthase may be down-regulated by Aspergillus toxin.

Common variable immune deficiency: respiratory manifestations, pulmonary function and high-resolution CT scan findings.

BACKGROUND: Common variable immune deficiency (CVID) is prone to under-diagnosis and may not reach relevant specialists until late in life. Morbidity is most commonly due to acute-on-chronic respiratory infections leading to respiratory failure. AIM: To investigate respiratory complications, lung function and high-resolution computerized tomography scan (HRCT) findings and mortality in 47 patients with CVID. SETTING: A regional immunology unit (Birmingham Heartlands Hospital). DESIGN: Retrospective observational case-note study following the introduction of shared care between immunology and respiratory medicine. RESULTS: Age at diagnosis ranged from 5 to 72 years, with a median time from development of first symptoms to diagnosis of 4.0 years. There was delay in referral between chest physicians and immunologists, (median referral time between specialities >5 years). Forty-two patients had respiratory complications, due to bronchiectasis (n=32), asthma (n=7), recurrent chest infections (n=9) without concomitant evidence of structural lung damage, and granulomatous lung disease (n=2). Spirometry was abnormal in 10/39 patients (7 obstructive, 3 restrictive). Bronchiectasis was confirmed on chest radiograph (n=9) and HRCT (n=24). Despite the high prevalence of bronchiectasis, few patients had received instruction in physiotherapy and sputum culture results were sparse. DISCUSSION: To reduce the morbidity associated with CVID, there needs to be greater awareness of respiratory complications, particularly amongst physicians caring for such patients. Emphasis has been placed on adequate dosage of immunoglobulin, but early involvement by a respiratory physician is essential to monitor lung function and initiate optimal therapy, to minimize the occurrence and progression of lung damage.

Occurrence and risk of cochleotoxicity in cystic fibrosis patients receiving repeated high-dose aminoglycoside therapy.

Cystic fibrosis (CF) patients receive repeated courses of aminoglycoside therapy. These patients would consequently be expected to be more susceptible to cochleotoxicity, a recognized side effect with single courses of aminoglycoside therapy. The primary aim of this retrospective study was to establish the incidence and severity of auditory deficit in CF patients. Standard (0.25- to 8-kHz) and high-frequency (10- to 16-kHz) pure-tone audiometry was carried out in 70 CF patients, and the results were compared with the results from 91 control subjects. These subjects were further divided into pediatric and adult groups. Of 70 CF patients, 12 (1 pediatric) displayed hearing loss considered to be caused by repeated exposure to aminoglycosides. There was a nonlinear relationship between the courses of therapy received and the incidence of hearing loss. The severity of the loss did not appear to be related to the number of courses received. Assuming the risk of loss to be independent for each course, preliminary estimates of per course risk of hearing loss were less than 2%. Upon comparison with previous clinical studies and experimental work, these findings suggest that the incidence of cochleotoxicity in CF patients is considerably lower than would be expected, suggesting that the CF condition may confer protection against aminoglycoside cochleotoxicity.

Extrapleural bronchial artery ligation for life-threatening hemoptysis in cystic fibrosis--a case report.

Hemoptyses are common in cystic fibrosis (CF) patients. They range from massive life-threatening (> 240 mL/24 hours) to recurrent minor streaking. Limited pulmonary reserve, potential concurrent chest infection, and the progressive nature of CF pose a high risk to this subgroup. Conservative management and selective bronchial artery embolization (BAE) control most acute episodes, but the recurrence rate is high. The possible need for lung transplantation in future makes an extrapleural approach for bronchial artery ligation desirable. The aim of this study was to assess the role of extrapleural bronchial artery ligation in the treatment of recurrent hemoptysis in CF patients. This is a retrospective analysis of four patients between 1986 and 1999 treated by extrapleural thoracotomy and ligation of bronchial arteries. Indications, surgical experience, and outcome are presented. Three patients underwent unilateral, and one patient bilateral extrapleural thoracotomy (in two separate sessions) for bronchial artery ligation. There were three men and one woman, with a mean age of 26.6 years (range 19-32 years). Indications were failure to stabilize the bronchial arterial catheter for BAE (three cases), recurrence after BAE previously controlled bleeding (one case), and communication with the right costocervical trunk signifying risk to the spinal circulation (one case). The mean follow-up was 68 months (range 3-144 months). There was one death in this series, a patient who was asphyxiated with hemoptysis, requiring ventilation preoperatively. He underwent successful extrapleural thoracotomy for bronchial artery ligation, with no further bleeding but succumbed to severe chest infection and multiorgan failure a few days later. Two patients had recurrent bleeding 12 and 36 months after surgery. Selective bronchial angiography proved the contralateral bronchial arteries to be the culprit. Extrapleural bronchial artery ligation is an effective method of controlling hemoptysis in CF, when BAE has failed. This approach minimizes pleural adhesions and is, therefore, desirable in the future consideration for lung transplantation. In this experience, muscle-sparing thoracotomy and postoperative epidural analgesia significantly improved the postoperative recovery.

A prospective study of nasal disease in adult cystic fibrosis.

Twenty-six adult cystic fibrosis patients were studied to compare nasal disease with their laboratory correlates including skin testing, immunoglobulin and Aspergillus fumigatus precipitin levels, saccharin testing and sputum cultures. Six patients were asymptomatic and all of these had negative skin tests, normal IgE levels and negative Aspergillus fumigatus precipitins. Thirteen patients had rhinitis, 12 had positive skin-testing for common allergens, 10 elevated IgE levels and nine positive Aspergillus fumigatus precipitins. Seven patients had polyps, all had normal IgE levels and negative Aspergillus fumigatus precipitins, six had positive skin testing for common allergens. There also appeared to be a relationship between Pseudomonas spp. colonization and positive skin testing.

The outcome of 72 pregnancies in 55 women with cystic fibrosis in the United Kingdom 1977-1996.

OBJECTIVE: To identify pregnancies in women with cystic fibrosis and describe obstetric, infant and maternal medical outcomes in relation to the severity of maternal disease. DESIGN: Retrospective study, based on casenotes. SETTING: Eleven cystic fibrosis centres in the United Kingdom. POPULATION: Pregnant women with cystic fibrosis. METHODS: Single observer medical and obstetric casenote review categorising maternal cystic fibrosis (e.g. genotype, pancreatic, hepatic and diabetic status) and pre-pregnant severity (e.g. weight and lung function) and noting fetal outcome and maternal morbidity. MAIN OUTCOME MEASURES: Completed pregnancies and pregnancy losses, fetal outcome and complications, maternal morbidity, such as changes in weight, lung function, pulmonary infections during and after pregnancy. Relation of outcomes to severity of maternal cystic fibrosis. RESULTS: From 72 pregnancies identified, the outcomes were known for 69; there were 48 live births (70%) of which 22 were premature (46%); 14 therapeutic abortions (20%); and 7 miscarriages (10%). There were no stillbirths, neonatal or early maternal deaths. Three major fetal anomalies were seen, but no infant had cystic fibrosis. At the conclusion of our study three pregnancies were still continuing. Prematurity with increased fetal complications and maternal morbidity with infection, declining lung function and poor weight gain were associated with poor pre-partum lung function. CONCLUSION: Pregnancy occurs in women with cystic fibrosis of all degrees of severity. Outcomes for the infant are generally good but are variable for the mother. Predicting outcome on the basis of maternal severity is difficult but lung function appears to be the most significant determining factor. Pregnancy may be normal in women with normal lung function (forced expiratory volume > 80%). However, it may adversely affect mild and moderate lung disease due to cystic fibrosis and should be avoided in pulmonary hypertension, cor pulmonale and when forced expiratory volume < 50% predicted. Ideally, all pregnancies should be planned with prior counselling and monitored by dedicated cystic fibrosis teams, including obstetricians who are experienced in managing high risk pregnancies.

Heart lung transplantation in a patient with end stage lung disease due to common variable immunodeficiency.

The case history is presented of a patient with common variable immunodeficiency in whom heart lung transplantation has been carried out with success. Transplantation was the only long term therapeutic option in this patient due to the progressive respiratory failure resulting from bronchiectasis, emphysema, and granulomatous lung disease.

Regional microbiology of the cystic fibrosis lung: a post-mortem study in adults.

Although the majority of patients with cystic fibrosis (CF) become chronically colonized with Pseudomonas aeruginosa, the mode of acquisition of infection remains unclear. Epidemiological studies using genotyping techniques suggest that person-to-person transmission of this organism may occur. All these studies have utilized sputum or throat swab samples. We have studied the regional microbiological flora of the lungs of five CF patients at post-mortem and genotyped P. aeruginosa strains found therein and in the major airway. We have shown that although in most cases major airway secretions accurately reflect the peripheral lung flora, in cases of multiple strain carriage, major airway cultures may not reflect all strains present in the periphery of the lung. This finding has implications for the interpretation of epidemiological studies that use genotyping of strains from sputum and throat swab samples to assess possible routes of transmission.

Long-term nasal intermittent positive pressure ventilation in patients with cystic fibrosis and hypercapnic respiratory failure (1991-1996).

In patients with cystic fibrosis (CF), nasal intermittent positive pressure ventilation (NIPPV) is currently used as a short-term bridge to transplantation but its precise role has yet to be determined. Patients were offered a therapeutic trial of NIPPV when candidates for lung transplantation, with respiratory failure unresponsive to medical treatment. Twelve patients, six male of mean age of 26 +/- 1.4 years, had a trial of NIPPV. At recruitment the mean percentage predicted forced expired volume in one second (FEV1) was 15.1% +/- 1.2%, arterial carbon dioxide (PaCO2) 8.7 +/- 0.6 kPa, arterial oxygen (PaO2) with variable FiO2 7.4 +/- 0.6 kPa and arterial bicarbonate (HCO3-) 40.1 +/- 1.6 mmol l-1. Ten cases tolerated NIPPV for 1-15 months, mean 5.1 +/- 1.4 months, with subjective improvement in headache and quality of sleep. At 3 months, there was significant improvement in forced vital capacity, PaCO2 and arterial HCO3- and there was a reduction in the number of hospital inpatient days (P < 0.05). Subsequently three cases had lung transplantation, four died on the active list and three are awaiting organs. Two patients failed to tolerate NIPPV owing to abdominal bloating and increasing hypercapnia. In conclusion, NIPPV, if tolerated, was a useful adjunct in the treatment of CF patients with hypercapnic respiratory failure awaiting transplantation. Further prospective studies are required to determine the optimum time to commence NIPPV and to clarify its precise role.

Ventilation in a Birmingham intensive care unit 1993-1995: outcome for patients with chronic obstructive pulmonary disease.

The aims of the study were to look at information on which the decision to ventilate chronic obstructive pulmonary disease (COPD) patients admitted to an intensive care unit (ITU) was based (including whether there was discussion with the patient, relatives and consultant), to identify indicators of poor prognosis, and to assess the outcomes of ventilation and functional capacity after discharge. A retrospective study of 27 months of admissions was carried out. The following variables were studied to see if they influenced prognosis: premorbid history, admission diagnosis, consultant involvement in the decision to transfer to ITU, admission chest radiograph, sputum bacteriology, arterial blood gases, APACHE II scores, duration of ventilation and complications in ITU. In-hospital mortality, post-discharge mortality and length of hospital stay were recorded. Functional capacity after discharge was assessed from the hospital clinic records and from general practitioners. Forty-six percent of case notes had inadequate premorbid information and no documented discussion occurred in 66% of patients/relatives. Poor prognostic indicators were admissions after cardiorespiratory arrest, cases discussed with consultants regarding ITU transfer, previous therapy with long-term oral steroids, and developing renal or cardiac failure in ITU. APACHE II scores were higher in the group that died. There was 49% hospital mortality and 59% 1-year mortality. Fifty-three percent of survivors were dependent upon carers and housebound, and general practitioners felt that 59% of survivors had a higher dependence on carers, a worse exercise tolerance and a poorer quality of life than before admission. The decision to ventilate is often made with inadequate background history, which could be sought from general practitioners, hospital case notes and family. There is significant morbidity and mortality following ventilation. Further prospective studies are required to help select which COPD patients should be ventilated.

Serum IgG response to an outer membrane porin protein of Burkholderia cepacia in patients with cystic fibrosis.

Early and accurate diagnosis of Burkholderia cepacia infection is important, particularly if segregation is to prevent patient-to-patient transmission. We have examined the serum response to a B. cepacia-specific 80-kDa outer membrane protein. 21 patients colonised with B. cepacia and Pseudomonas aeruginosa for 2-51 months (mean 11 months) were age- and sex-matched with 21 patients colonised with P. aeruginosa but not B. cepacia. The 80-kDa protein was recovered by electroelution from outer membrane proteins, separated by SDS-PAGE, coated onto ELISA plates, reacted with patient sera diluted 1:200, protein A-peroxidase and chromogenic substrate. We found that 19/24 patients colonised with B. cepacia and P. aeruginosa had high values, 2/24 patients had intermediate values, and 2/24 patients had a low value. 20/21 patients colonised with P. aeruginosa alone had low values and 1/21 had an intermediate value. We found that in the longitudinal serum samples studied from four patients only one patient developed high values after the first isolation of B. cepacia suggesting that seroconversion does not occur immediately after the first sputum culture of B. cepacia. We conclude that an ELISA test using B. cepacia-specific 80-kDa outer membrane protein can distinguish B. cepacia colonised and non-colonised patients and may be useful in the early diagnosis of B. cepacia infection.

Distinction between pleural mesothelioma and pulmonary adenocarcinoma using MOC31 in an asbestos sprayer.

Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may pre-dispose to malignant mesothelioma and other neoplasms. The occurrence to two primary tumours in the same patient is rare, and the appearance of a pleural mesothelioma and another lung tumour is exceptional. The present case report describes a patient who, by standard immunohistochemistry, was thought to have mesothelioma at pleuro-pneumonectomy, and adenocarcinoma in the other lung at post-mortem 5 months later. Subsequent investigation using the MOC31 antibody demonstrated a single pathology of adenocarcinoma of the lung. The additional use of this antibody has important histopathological and legal implications.

Severe lipoid pneumonia following attempted suicide by mineral oil immersion.

Following an attempted suicide by drowning in a vat of mineral oil, a previously fit man survived the usually fatal lipoid pneumonia resulting from total immersion after intensive support and prolonged steroid therapy with recovery of chest radiography and pulmonary function at one year.

Outcome for patients colonised with Burkholderia cepacia in a Birmingham adult cystic fibrosis clinic and the end of an epidemic.

BACKGROUND: There has been increasing concern since 1979 about the emergence of Pseudomonas cepacia (Burkholderia cepacia) in patients with cystic fibrosis in the UK and elsewhere. Colonisation of the sputum has been shown to be associated with increased morbidity and mortality. Evidence suggests person to person transmission and some centres have segregated those colonised with B cepacia from other patients with cystic fibrosis. The outcome of patients colonised by B cepacia has been studied, together with the effects of strict segregation. METHODS: The outcome in 18 patients with sputum colonised by B cepacia was compared with that in age, sex, and severity matched controls with no evidence of B cepacia colonisation by a retrospective case note study. RESULTS: No difference between cases or controls were found in the 24 month period prior to colonisation by B cepacia in lung function, number of days in hospital, or outpatient visits. Colonisation led to an increased rate of loss of lung function and utilisation of hospital services. There was an increase in the numbers of transplants and deaths amongst the cases. Since 1992 there have been only three new cases of B cepacia colonisation and the incidence and prevalence of the organism has fallen dramatically since segregation commenced. CONCLUSIONS: B cepacia appears to be linked to the decline in colonised individuals. There was no evidence that colonisation occurred in patients declining for other reasons. B cepacia colonisation confers a worse prognosis than Pseudomonas aeruginosa alone. Segregation appears to limit the spread of the organism from infected individuals to other patients with cystic fibrosis.

Referral for lung transplantation: experience of a Birmingham Adult Cystic Fibrosis Centre between 1987 and 1994.

BACKGROUND: Whilst much is known of the outcome of lung transplantation for patients with cystic fibrosis, less is known about those patients who are either not referred for transplantation or who die before a donor is available. The referral practice and outcome of all the cystic fibrosis patients in one clinic was documented, whether or not they were assessed for lung transplantation. The results give a perspective on the impact of the current transplantation programmes on the adult cystic fibrosis population as a whole. METHODS: A retrospective study was made of patient deaths and referrals for lung transplantation between 1987 and 1994 from the Adult Cystic Fibrosis Clinic at Birmingham Heartlands Hospital. RESULTS: The Birmingham Heartlands Adult Cystic Fibrosis Clinic has managed 192 patients since its beginning and currently cares for 141 patients. Since 1987 there have been 16 deaths in patients with cystic fibrosis who were considered unsuitable for lung transplantation. Of 49 patients referred for lung transplantation, 47 were accepted on to a provisional or active waiting list. The mean (SE) age at referral was 23.9 (0.7) years and mean (SE) forced expiratory volume in one second (FEV1) was 0.87 (0.04) 1. Fourteen patients died whilst awaiting transplantation and 19 received donor lungs. There have been 10 deaths in the transplanted group. Survival following transplantation was 58% at one year and 52% at two years. CONCLUSION: Most of the deaths that occurred in the Cystic Fibrosis Clinic were in patients who either were not considered suitable for transplantation or were still awaiting transplantation. Whilst lung transplantation is the focus for many adults with cystic fibrosis, lack of donor organs has limited the impact of transplant programmes on the clinic.

Treatment of pulmonary aspergilloma in cystic fibrosis by percutaneous instillation of amphotericin B via indwelling catheter.

Pulmonary aspergilloma is a rare complication of cystic fibrosis and is a contraindication to transplantation. The elimination of an aspergilloma in a 24 year old patient with cystic fibrosis by percutaneous instillation of amphotericin B is described, enabling her to be accepted on a lung transplantation programme.