Outcome in Adult Bronchiectasis

Abstract

The outcome in adult bronchiectasis has not been well described; in particular there has been a lack of long-term prospective studies. Therefore a follow-up study was performed to assess outcome in bronchiectasis in a cohort of adult patients. One hundred-and-one sequential adults, 33 male and 68 female; age 54 ± 14 years (mean ± SD) with bronchiectasis had a clinical assessment and spirometry performed. All were non-smokers and 84 were classified as having idiopathic disease. Patients were commenced on a standardized treatment regime and followed up for a minimum period of 2 years. On their last review when patients were clinically stable, a repeat clinical assessment and spirometry was performed and compared with the initial review. The primary endpoints measured were symptoms and FEV₁. Subjects were followed up for 8.0 ± 4.9 years. Clinical review showed that the patients had persistent symptoms that, in the case of dyspnea and sputum volume, were worse on follow-up. Spirometry showed a significant decline in FEV₁ over the follow-up period with an average loss of 49 ml per year. This study showed in this group of predominantly female adult patients with bronchiectasis followed up for 8 years, patients had persistent symptoms and an excess loss in FEV₁.

• Bronchiectasis
• Outcome assessment
• Signs and symptoms
• Spirometry

Introduction

Bronchiectasis is a condition that prior to the introduction of antibiotics was associated with a mortality rate of over 30% with patients generally dying before they were 40 years old [[1]]. In the antibiotic era the mortality rate from bronchiectasis fell dramatically and this led to the condition being labelled in the late 1980s as being an “orphan disease” [[2]]. The recent advent of high resolution computerized tomography (HRCT) scanning has made the diagnosis of bronchiectasis considerably easier and there has been a renewed awareness of this disease, which remains a significant cause of respiratory morbidity.

In the antibiotic area there have been very few studies that have assessed the outcome of bronchiectasis. Field followed up a cohort of children with bronchiectasis from 1949 over 20 years. She found that while mortality was significantly less, subjects still had persistent bronchial sepsis [3&4]. A retrospective trial performed in 1981 [[5]] reviewed the files of 116 patients who had been diagnosed as having bronchiectasis of at least 5 years previously with a mean follow-up of 14 years. Twenty-two of the subjects had died, and the survivors were interviewed and the findings compared with the initial file results. This article's conclusion was that the survivors had a reasonable quality of life and there had not been a significant deterioration in respiratory function in most patients. One study [[6]] assessed the mortality rate by reviewing a national database and one prospective study reviewed theeffect of DNAase on patients treated with this medication for a period of 18 months [[7]]. There is little information available for the physician to assess the outcome of a patient with bronchiectasis and to identify which factors are important in affecting prognosis.

To assess the outcome of bronchiectasis a longterm follow-up study was performed on a cohort of adults with bronchiectasis. The cohort consisted of subjects presenting to Monash Medical Centre with bronchiectasis. A large group of patients with bronchiectasis were recruited, commenced on a standardized treatment regime, and followed up prospectively for an average period of 8 years, with regular thoracic physician review. The primary endpoints measured were symptoms and forced expiratory volume in 1 second (FEV₁).

Materials and Methods

Study Population

A cohort of 149 patients who presented to the Respiratory Medicine Department at Monash Medical Centre (MMC) was assessed between 1980 and 2001. These patients had all had their bronchiectasis radiologically confirmed (by CT or bronchogram) with the films being reviewed by a consultant radiologist and bronchiectasis was diagnosed when there was bronchial dilatation and lack of tapering. The majority of these subjects (126 patients, 84%) were referred to MMC by their local family doctor, who felt that patients needed the expertise of a pulmonary physician for investigation. The other major source (16 patients, 9%) was from hospital discharge. This cohort of patients represents a sequential series. Subjects who were current smokers or had smoked in the past year were excluded (15 subjects). The rationale for excluding smokers is that the investigators wished to exclude the confounding effect of tobacco on the subjects' clinical status and lung function. Twelve subjects were lost to follow-up, 16 subjects were not able to attend for re-assessment and 5 subjects died before they were reassessed. This left a group of 101 subjects.

More information was obtained about the characteristics of this cohort of 101 patients including thoracic surgical procedures, ear, nose, and throat (ENT) interventions and the onset of respiratory symptoms.

When the patients were first seen at MMC of the 101 subjects 8 had a bronchogram and 93 had a CT scan to diagnose their bronchiectasis. At the time of initial review the average number of lobes showing changes of bronchiectasis was 2.5 ± 1.1 (mean ± SD). Subjects all eventually had HRCT scans performed. To confirm the presence of bronchiectasis and to define the extent of the disease the most recent HRCT scans were obtained and scored using a standardized method [[8]], which has been used in several studies that have assessed subjects with bronchiectasis [[9]]. This technique involves scoring each lobe for bronchiectasis with 0 given for no bronchiectasis, 1 given for 1 segment with bronchiectasis (bronchiectasis was defined as being present by either; 1) the internal diameter of the bronchus as being wider than its adjacent artery or 2) failure of the bronchi to taper), 2 for 2 or more segments with bronchiectasis, and 3 for a lobe with cystic fibrosis. The lingula was counted as a lobe so the score ranged from 0 to 18. If a subject had had a lobectomy, the total possible score was reduced to 15. The final score was calculated as the raw score divided by the total possible score and then multiplied by 100 (e.g., 6/15 × 100 = 33).

Procedures

On the initial assessment when patients were clinically stable (i.e., living independently and were assessed when at their usual baseline state and had not had an exacerbation for at least 1 month), subjects were asked about the presence, frequency, and volume of productive cough (sputum volume was estimated by comparison with a teaspoon (5 ml), tablespoon (15 ml), eggcup (50 ml), and teacup (150 ml)). Details were obtained about presence of rhinosinusitis, chest pain, hemoptysis in the past year, fatigue, frequency of exacerbations (defined by increase in sputum volume, dyspnea, or fever) and symptoms of dyspnea using the Medical Research Council (MRC) dyspnea grade. The diagnosis of exacerbation was made when one of these factors was present and the patient reported a worsening in their condition. Subjects were educated about exacerbations. Subjects were asked about their general health, previous tobacco consumption, and factors associated with bronchiectasis. Findings on physical examination were also recorded. The data was collected by two respiratory physicians (PK and PH), who took a standardized history from each patient.

Subjects had spirometry performed for FEV₁, forced vital capacity (FVC), and bronchodilator (BD) response to inhaled salbutamol at MMC. At least two measurements differing by less than 5% from each other had to be produced. The largest volume was used in the analysis. The spirometer used was a Jaeger pneumotach system that was calibrated daily with a 2-liter syringe. Before 1990, 15 subjects had their initial spirometry performed using a Morgan rolling seal spirometer that was calibrated daily. All spirometry was done by trained respiratory scientists. It is acknowledged that the diagnoses of asthma and COPD can be difficult to separate out from bronchiectasis. Both diagnoses were made by a respiratoryphysician with features of asthma being intermittent symptoms, airway reversibility, atopy, and response to salbutamol with features of COPD being history of smoking, CXR appearance, and decreased lung diffusion.

Patients were also asked to produce a sputum sample that was analysed for microscopy and culture (bacteria and fungi and 55 subjects had analysis for the presence of mycobacteria). To assess for predisposing factors for bronchiectasis, all subjects had blood taken for full blood examination and immunoglobulin levels. Screening was also undertaken for cystic fibrosis (multiple mutation analysis/sweat testing), ciliary function (done for unexplained infertility), alpha1-antrypsin levels, and allergic bronchopulmonary aspergillosis (ABPA), (aspergillus precipitins and skin test reactions).

Patients were commenced on a treatment regime consisting of antibiotics for exacerbations, chest physiotherapy, bronchodilators, and vaccinations (Table 1). Patients were followed up on a regular 1- to 2-year basis through Monash Medical Centre by the investigators who provided ongoing care.

Table 1.  Treatment Regime for Bronchiectasis Patients.

Antibiotics

Used for exacerbations, not given as maintenance therapy, not broad spectrum

Vaccinations

Influenzae vaccination (yearly) and patients encouraged to have Pneumococcal vaccine (3–5 yearly)

Bronchodilator

Salbutamol ± ipratropium taken as required for symptom relief

Referral to physiotherapist

Patients showed techniques; including postural drainage, breathing exercises, and oscillating PEP devices and encouraged on every review to keep up with physiotherapy

Bronchiectasis is a heterogeneous condition and there were some changes in the treatment over a 20-year period. The antibiotics used were most commonly a narrow spectrum penicillin/cephalosporin, a macrolide or tetracycline, the choice being made on previous sputum results and patient tolerance. The antibiotics were given for 10 to 14 days. If the subject had grown Pseudomonas on multiple occasions previously, ciprofloxacin was given. For hospitalizations patients were treated with a narrow spectrum penicillin/cephalosporin unless they had a resistant organism (in which case they were usually treated with an aminoglycoside).

Over the period of the data collection a variety of physiotherapy airway clearance techniques were employed. Initially patients were taught methods of postural drainage and manual techniques (e.g., percussion) with instructions to carers for use at home. From 1990 independently performed airway clearance techniques were introduced, including the Active Cycle of Breathing, positive expiratory pressure (PEP), and oscillating PEP devices (e.g., flutter valves). It is acknowledged that whilst all patients attended a physiotherapist for treatment and instruction regarding a home physiotherapy program, it was difficult to accurately quantify adherence.

Subjects with a diagnosis of asthma were treated with inhaled corticosteroids (ICS) [10&11]. Bronchodilators were taken as inhaled medication on as required basis, two to four times a day. One subject who had common variable immune-deficiency received monthly immunoglobulin infusions, and one subject with mycobacterium avium complex (MAC) was treated with 18 months' of appropriate antibiotics.

To assess the outcome in this cohort all subjects were reviewed at least three times and followed up for at least 2 years by one of the authors. On the final review when patients were clinically stable, a repeat clinical review and spirometry was performed and compared with the initial assessment.

The FEV₁ has been shown to be the most important measure of outcome in COPD [[12]]. FEV₁ has not been reported in detail in the context of bronchiectasis but it is an important measurement of lung function in this condition. A number of factors have been shown to affect FEV₁ in COPD [[13]]. In this study factors that have been shown to affect the outcome of FEV₁ in COPD were assessed in addition to specific factors associated with bronchiectasis. The factors were; volume of sputum, duration of chronic productive cough, frequency of exacerbations, history of smoking, airway hyperresponsiveness/significant BD effect (defined as > 15% improvement in FEV₁ after inhaled salbutamol with a volume of at least 200 ml), and type of bacteria isolated from sputum. These factors were correlated with the FEV₁ in subjects with bronchiectasis.

Statistical Analysis

Statistical analysis was performed using either Stata SE 8.0 (College Station, Texas) or Prism 2 (San Diego, California, USA) software. Conventional descriptive measures of the middle (e.g., mean) and spread (e.g., standard deviation), were derived for continuous variables, as well as cross-tabulations for categorical variables. Comparisons between groups of variables were accomplished using methods appropriate for the variable scale and distribution. The major outcome of interest was the change in FEV₁ between initial assessment and follow-up review, expressed in mls per year. Adjustment for potential confounders was performed using multi-variable linear or logistic regression methods. In all analyses, a Type I error rate (the probability of detecting a statistically significant association when none exists) was set at 5%. This study was approved by the Ethics Committee at MMC and informed consent was obtained from the patients.

Results

Characteristics of the Patient Cohort

Eighteen of the subjects had lobectomies and 4 had had thoracotomies for treatment of lung abscesses. Over half the cohort (54 subjects) had been reviewed by an ENT surgeon, 24 of them had had ENT surgery, and 51 of them had either surgery or X-rays showing evidence of sinusitis. Seventy-five of the subjects had had the onset of chronic respiratorysymptoms from childhood. These symptoms were most commonly chronic productive cough, recurrent significant chest infection, and rhinosinusitis. Most subjects (76) had had chronic respiratory symptoms for more than 20 years before they were assessed for this study. Fifty-two of this cohort were diagnosed as having bronchiectasis at the start of this review (i.e., new diagnoses).

Follow-up data of at least 2 years was obtained on 101 subjects with a mean length of follow up of 8.0 ± 4.9 years (Table 2) with an average age of 54 years at the initial assessment. The median follow-up was 7 years with a range of 2 to 22 years. All subjects had a comprehensive clinical review and spirometry on initial assessment and final follow-up review. The total number of reviews of this group through MMC was over 1000. The subjects were predominantly female, otherwise generally well and living independently. This cohort had a relatively low incidence of co-morbid illness (shown in Table 2). Three of the subjects had had a cerebrovascular accident (CVA) from which they had made a good recovery. Seven subjects had a history of reflux for which they were on acid suppressant medication and this not associated with their respiratory symptoms. Eleven subjects had a diagnosis of asthma and five had a diagnosis of COPD.

Table 2.  Demographics/Co-Morbidities of 101 Patients.

Period of follow-up (years)	8.0 ± 4.9 (mean ± SD)
Age (years)	54 ± 14 (mean ± SD)
Sex ratio of group	33 male 68 female
Ex-smokers	20 patients
HRCT score	33 ± 21 (mean ± SD)
Co-morbidities
Asthma	11 patients
COPD	5 patients
Ischemic heart disease	9 patients
Hypertension	12 patients
Cerebrovascular disease	3 patients
Esophageal reflux	7 patients
Rheumatoid arthritis	2 patients

Screening for underlying causes of bronchiectasis demonstrated that 10 of the subjects were classified as having post-infectious bronchiectasis (defined as chronic cough, and sputum production directly after pneumonia, tuberculosis, whooping cough, or measles). Three patients were diagnosed as having ABPA, one with common variable immuno-deficiency, and one with Young's syndrome. Two of the subjects had a diagnosis of rheumatoid arthritis but in both cases patients had bronchiectasis before the onset of this condition. Thus 84 of the subjects were classified as having idiopathic disease. The number of subjects on ICS was 47 subjects. A short course of oral corticosteroids were used for exacerbations where there was felt to be a significant component of bronchospasm. Prolonged treatment with oral corticosteroids was used in 3 patients who had ABPA.

Symptoms

Most patients on initial review had significant symptoms. Ninety-nine of the 101 subjects had a history of chronic productive cough. Sputum was generally mucopurulent and the average volume of sputum produced was 32 ± 29 ml. Most patients on close questioning described recurrent upper respiratory tract symptoms, present for more than a year with a range in severity from nasal drip to severe pansinusitis, which were classified under the general symptom of rhinosinusitis. Most patients also complained of dyspnea, which was generally mild with a mean MRC dyspnea score of 1.9. Thirty-one of the subjects complained of hemoptysis in the past year and 22 described chest pain. Fatigue was also a prominent symptom in most patients (70 patients). Physical examination showed 87 patients had crackles, 6 had wheeze, and 1 was clubbed.

Follow-up review was taken as the last visit where patients were seen and were clinically stable (no exacerbation in the past month, outpatient setting). Patients had a repeat clinical interview and examination. Most patients continued to have significant symptoms (Table 3). The MRC dyspnea score and sputum volume were significantly worse on follow-up (p < 0.05, paired t-test).

Table 3.  Symptoms; Initial Assessment and Follow-Up Review.

	Initial review (n = 101 patients)	Follow-up (n = 101 patients)	p
Symptoms
Productive cough	98%	93%
Daily sputum	69%	72%
Rhinosinusitis	72%	79%
Hemoptysis	31%	21%
Hospitalization	24%	32%
Fatigue	69%	79%
Daily sputum (mls)	32 ± 29 mls	47 ± 34 mls	p < 0.05
MRC dyspnoea score	1.9 ± 1.1	2.8 ± 1.3	p < 0.05
Signs
Crackles	86%	63%
Wheeze	6%	12%
Clubbing	1%	1%

The number of patients who did not produce daily sputum was on initial assessment was 14 and on follow-up review the number was 12. The number of subjects who coughed up more than 60 mls of sputum a day on initial assessment was 21 patients and on follow-up review was 25 subjects. The number of patients with no dyspnea was on initial review was 31 and on follow-up review was 31. The number of subjects with MRC grade 4 to 5 dyspnea on initial assessment was 13 and on follow-up review was 20.

Spirometry

Spirometry was performed on initial review and final follow-up visit. Initial review showed that the typical pattern was a mild obstructive pattern with an FEV₁ of the group being 72% of predicted values (1.87 litres), and 25 patients had > than 15% reversibility [[14]] in response to bronchodilator (Table 4). In the follow-up period the FEV₁ of the group declined to 61% of predicted (1.49 litres). This averaged out over the 8-year follow-up period as being a decline in FEV₁ of 48.8 mls per year, with the change in males being 56.9 mls per year and in females it was 44.0 mls per year. In healthy middle-aged adults the normal rate of decline is approximately 30 mls per year for men and 25 mls per year for women [[13]]. This finding was reinforced by comparing the percent predicted values for FEV₁ of the group on initial review and follow-up. On initial review the FEV₁ percent predicted of the group was 72.2% and after 8 years it had fallen to 61%, a fall of more than 1% predicted per year.

Table 4.  Spirometry; Initial Assessment and Follow-Up Review.

Spirometry	Initial review (n = 101 patients)	Follow-up (n = 101 patients)
FEV1
Litres (mean and SD)	1.87 ± 0.68	1.49 ± 0.64
% predicted (mean and SD)	72.2 ± 25.0	61.2 ± 24.3
FVC
Litres (mean and SD)	2.79 ± 0.92	2.38 ± 0.79
% predicted (mean and SD)	86.1 ± 21.8	76.4 ± 21.4
FEV1/FVC
	67.0	63.7
BD effect > 15% (patients)	24	22

Mortality

Eleven of the 101 subjects of this cohort died in the follow-up period. The mean age of death was 73 years. The age predicted death rate for a group of this size and age living in Australia followed-up for 8 years is 7 deaths [[15]]. Six of the 11 subjects died of progressive respiratory failure as a direct consequence of their bronchiectasis. Subjects who died had a significantly worse FEV₁ than survivors (p < 0.01) with a mean average FEV₁ of 39 ± 14% predicted and an FVC of 59 ± 17% predicted.

Factors Associated with Excessive Decline in FEV₁

Multivariate analysis was used to assess the decline in FEV₁ with factors on initial assessment of; age, sex, volume of sputum, type of bacteria, past history of smoking, bronchodilator effect, and frequency of exacerbation. A significant association was found between volume of sputum (p < 0.003) and decline in FEV₁ (i.e., > than the average decline of the group). There was a trend for BD effect (p = 0.075) and exacerbations (p = 0.132) to be associated with excess decline in FEV₁.

Sputum

On initial assessment, the most common pathogenic isolates were Haemophilus influenza present in 44 patients followed by Pseudomonas aeruginosa [10], Staphylococcus aureus [8], Streptococcus pneumoniae [5], Moxarella catarrhalis [3], and 1 subject had MAC isolated. Thirty-one patients had no pathogens isolated from their sputum. All of the subjects had sputum analysed.

As a secondary outcome measure, the files of the patients were reviewed and data for the most recent sputum microbiology result recorded. Ninety-four of the 101 subjects had a follow-up sputum analysis performed. The period of follow-up was 6.5 ± 3.4 years (mean ± SD). The pathogens isolated were fairly similar with Haemophilus influenzae again the most common isolate present in 38 patients, followed by Pseudomonas aeruginosa [18], Staphylococcus aureus [5], Streptococcus pneumoniae [4], and Moraxella catarrhalis [5]. Thirty patients had no pathogens isolated from their sputum.

Discussion

Most of the patients in this cohort were female and the bronchiectasis was generally idiopathic. These findings have been reported in other studies [[9]][[16]]. The majority of the patients had symptoms that dated from childhood similar to another recent study [[9]]. As has been the case with other recent studies, the majority of the patients had idiopathic disease [[9]][[16]]. On initial review most patients had quite significant symptoms with the dominant complaints being productive cough and fatigue. Rhinosinusitis was also a common complaint, a feature that has not been highlighted in most studies. It should be emphasized that subjects with rhinosinusitis had a considerable range in their symptoms from a post-nasal drip to fulminant pansinusitis. Spirometry showed mild airway obstruction and most patients had multi-lobar disease. Similar to previous studies [[17]] the most frequently isolated bacterium was Haemophilus influenzae.

On review patient's symptoms were essentially unchanged and the majority of them still complained of persistent symptoms. The sputum volume and dyspnea had become worse and this was reflected by a worsening in spirometry. One other recent study [[16]] found in a cohort of 123 subjects that only 1 patient was clubbed. A study published in 1949 by Elaine Field [[3]] of 160 children with bronchiectasis found clubbing to be present in 43% and its presence was directly related to the presence of months of untreated fever. A follow-up study performed by Field in 1961 [[4]] found that clubbing had disappeared in 69% of patients in whom this had been initially reported, which she attributed to the influence of antibiotics. Fifty-one patients had reported having an episode of hemoptysis at some stage in their illness. The presence of hemoptysis in non-smokers should arouse suspicion of underlying bronchiectasis.

The FEV₁ of the group after an 8-year follow-up period fell from 1.87 litres to 1.49 litres or 49 ml per year. The excess decline in FEV₁ was also reflected by the comparing the percent predicted changes of the group at the beginning of 72% with the 8-year follow-up of 61% reflecting a excess fall in percent predicted values of more than 1% per year. This decline in FEV₁ in susceptible smokers who develop COPD is from 50–75 ml per year [[13]] and most subjects have generally been male. Therefore the decline in lung function in this group of non-smoking, predominantly female patients was comparable to smoking patients with COPD.

The factors that contribute to airway obstruction in bronchiectasis are still not clearly defined. The most distinctive feature of bronchiectasis, airway widening, would not be expected to produce significant airway obstruction. Recently one study found evidence that the predominant mechanism for airway obstruction in bronchiectasis came frominflammation causing edema/thickening of the small airways [[18]]. Bronchial thickening as measured on HRCT has been shown to be an important determinant of outcome in bronchiectasis [[19]]. This group of subjects with bronchiectasis had a progressive decline in airway function. This suggests that the ongoing symptoms of these patients reflects airway inflammation, presumably having its dominant effects in the smaller airways to produce progressive disease.

The factor that was most clearly associated with decline in FEV₁ was volume of sputum production, and this may be associated with the degree of bacterial inflammation in the lung. A recent article has shown that bacterial load as assessed by sputum analysis and IL-8 levels is directly correlated with deterioration in FEV₁ in COPD [[20]]. Bacterial colonization has been shown to be associated with decreased lung function in cystic fibrosis [[21]] and bronchiectasis [[22]]. In addition colonization with H. influenzae has been demonstrated to be associated with increased airway inflammation in subjects with chronic bronchitis [[23]]. The Copenhagen Study found that chronic mucus hypersecretion was associated with an excess decline in FEV₁ of 22.8 ml/year in men and 12.6 ml/year in women [[24]]. Bacterial colonization is associated with mucus secretion [[25]] and patients with mucus secretion have more airways inflammation [[26]]. However the role of bacterial infection in COPD remains controversial [[27]].

A history of significant bronchodilator effect had a trend to be associated with low FEV₁. In COPD, airway hyperresponsiveness is known to be associated with decreased respiratory function. The frequency of exacerbations also showed a trend to be associated with excess decline in respiratory function. There was not an association between specific bacteria and decline in FEV₁, although the small numbers for most bacterial types would affect statistical analysis. A past history of smoking was not associated with decline in FEV₁, as would be expected as none of the patients smoked in the review period.

In this large and varied cohort there were confounding factors that needed to be considered. Firstly bronchiectasis is a heterogenous condition with a number of causes and associations, all of which would affect outcome. In this cohort most of the patient cohort had idiopathic disease and the numbers of patients with other conditions was too small for statistical analysis. The next factor to consider was the effect of treatment and patient's compliance and follow-up. On follow-up review, over 80% of patients stated that they had continued to take antibiotics for exacerbations, take bronchodilators, and perform physiotherapy for exacerbations but the level of this compliance was difficult to quantify accurately. There were also some changes with the treatment regime over the 20-year period. Only half of the group were treated with ICS but there was no significant difference in any of the outcome parameters in subjects who were on this medication. There is also the issue of what might have happened if the patients had not had a diagnosis and ongoing medical treatment. Due to ethical issues it was not possible to have half the group treated and half not.

The issue of whether a 2-year follow-up is sensitive enough is not clear, but there appears to be no definition in the literature about what constitutes an appropriate length of time. Changes in spirometry probably require a longer-term follow-up than clinical review. The St. George Respiratory Questionnaire has been validated in 2 articles [28&29], for a 6-month follow-up. The two recent studies that have assessed the outcome of an intervention on adult bronchiectasis assessed subjects over an 18-month [[7]] and a 2-year period [[30]] respectively, with the primary outcomes being FEV₁ and clinical status.

Ideally all the patients should have been followed up for the same length of time as in classic studies like that performed by Fletcher and Peto [[12]], where subjects were followed up for 8 years to assess the effect of smoking. Unfortunately with a less common condition like bronchiectasis it was extremely difficult to simultaneously assemble a large cohort to follow up for a long period. Therefore subjects were recruited over a 22-year period. As a consequence there was a range in the follow-up period of this cohort but at 8 years on average this was similar to important studies that have measured outcome in COPD [[12]][31&32]. It is known that spirometry performance does vary in subjects by as much as 200 ml [[13]] and ideally spirometry should have been performed every year. However there have been widely accepted outcome studies in COPD that have assessed FEV₁ at only the beginning and end of the study [[24]][[33]].

Other measures could have been used to assess outcome such as radiological screening and comparison of CT scans. Unfortunately as CT scanning technology changes so quickly it was not possible to compare films as they were done with different machines using different techniques. Quality-of-life measurements would certainly be useful but these have only recently been validated in bronchiectasis. Nearly all subjects were able to walk satisfactorily so the 6-minute walk test was not so helpful. Measurements of right heart function could have been used for the patients with more severe disease.

There is limited data on the effectiveness of any treatments in bronchiectasis. The Cochrane reviews have assessed nearly all aspects of treatment in bronchiectasis. Cautious recommendations are only made for 2 of the 13 treatment modalities reviewed; long-term antibiotics in some patients [[34]] and the use of the inhaled mannitol [[35]]. Our own feeling is that bronchiectasis is a heterogenous condition and treatment needs to be tailored to each individual patient. Prompt treatment of infections seems important. Perhaps the biggest factor is the motivation of each patient to maintain their physical fitness and self-manage their disease. In the long term, better outcomes may be obtained by more targeted use of appropriate antibiotics, vaccinations, and possibly immune mediators.

Some of the patients in this cohort died. The death rate was not significantly higher than would be predicted in a cohort of this age followed up for this period but the primary cause of death in six of the subjects was bronchiectasis. One recent Swedish study that assessed the mortality rate in bronchiectasis found a higher death rate of 13% [[6]]. However this study also found a higher death rate from asthma than the Australian population. The reasons for this discrepancy are not clear. The numbers in this cohort were too small to exclude a type II statistical error.

The studies of Field commenced at the beginning of the antibiotic era found that the onset of late adolescence and early adulthood was associated with a marked improvement in symptoms that (with the exception of antibiotic treatment) appeared independent of any treatment given. Most of the cohort of subjects in the current study were born in the same period as those in Field's studies and are now middle-aged to elderly and are developing progressive disease. This pattern of improvement in adolescence/early adulthood and deterioration commencing from middle age may be the natural history of bronchiectasis in the antibiotic era.

In conclusion, bronchiectasis is a condition that in the pre-antibiotic era was associated with a high mortality rate. The introduction of antibiotics has clearly changed the nature of the condition, as has the recent introduction of HRCT to diagnose bronchiectasis. There is a lack of published information on the outcome of this important condition. In this cohort of 101 subjects followed up for an average period of 8 years, most subjects had significant ongoing symptoms and excess decline in lung function despite medical therapy. The results suggest that while outlook for subjects with bronchiectasis has improved, there is still a lot to be done to help such patients.

Acknowledgments

We thank Mr. Paul Guy of the Respiratory Function Laboratory at MMC for his advice and help.