(Chest. 2004;125:1815-1820.)
© 2004
American College of Chest Physicians
Survival of Patients With Bronchiectasis After the First ICU Stay for Respiratory Failure*
Mathieu Dupont, MD;
Arnaud Gacouin, MD;
Hervé Lena, MD;
Sylvain Lavoué, MD;
Graziella Brinchault, MD;
Philippe Delaval, MD, PhD and
Rémi Thomas, MD, PhD
* From the Service de Réanimation Médicale et Maladies Infectieuses, Service de Pneumologie, Centre Hospitalier Universitaire de Rennes, Rennes, France.
Correspondence to: Mathieu Dupont, MD, Service des Maladies Infectieuses et de Réanimation Médicale, Hôpital Pontchaillou, Rue Henri Le Guilloux, 35033 Rennes Cedex, France; e-mail: mathieu.dupont{at}chu-rennes.fr
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Abstract
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Study objectives: Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied.
Design: We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded.
Measurements and results: Forty-eight patients (mean age ± SD, 63 ± 11 years; mean simplified acute physiology score [SAPS] II, 32 ± 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival.
Conclusions: We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.
Key Words: bronchiectasis • intensive care • respiratory failure • survival
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Introduction
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Bronchiectasis was first described in 1819 by Laënnec1 as an irreversible dilatation and destruction of airways associated with chronic bacterial infection. The exact prevalence of bronchiectasis is unknown but has declined in developed countries with the immunization against pertussis and measles and the improved control of tuberculosis.23 In addition, advances and greater use of antimicrobial treatment and physiotherapy have led to an increased survival of patients with bronchiectasis.4 Nevertheless bronchiectasis is a disease with the potential to cause devastating illness, including respiratory failure (RF) requiring admission in an ICU. To our knowledge, there is no published study focusing on the survival of patients with bronchiectasis after the first ICU stay for RF.
In order to assess the long-term outcomes and to identify the factors associated with a reduced survival, we performed a retrospective observational study over a 9-year period on 48 consecutive patients with bilateral bronchiectasis admitted for the first time to the ICU for RF. Patients with confirmed cystic fibrosis were excluded from the study.
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Materials and Methods
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Patients
All adults with bronchiectasis admitted between January 1990 and March 1999 to the medical ICU at Rennes University Hospital were identified from admission records. The outcome was survival at March 1, 2000, which was used as the end of the study period to ensure that all patients had a potential of 1 year of observation time. Medical records were reviewed to ensure that cough and sputum production were reported by patients at least 5 years before the admission to ICU. In addition to the above symptoms, the diagnosis of bronchiectasis required that a high-resolution CT scan performed before ICU admission showed dilatations of airways lumens important enough to render their diameter larger than nearby vessels.5 Other CT abnormalities specific for bronchiectasis such as cysts, varicose constrictions along airways, bronchial wall thickening, or lack of tapering of airways toward the periphery were noted.678 The predominant type (ie, cylindrical, varicose, or cystic according to the Reid classification9) of bronchiectasis was noted. Lingula was considered as a separate lobe, making six lobes in all. The chest radiographs obtained just before ICU admission and/or those performed on ICU admission were reviewed to ensure that bilateral dilated and thickened airways were visible. Patients with confirmed cystic fibrosis, patients admitted for a reason other than RF, and those with unilateral bronchiectasis were excluded from the study. In addition, because we did not use noninvasive ventilation (NIV) as ventilatory support in patients with bronchiectasis and with RF before 1990, patients admitted prior to January 1990 were excluded.
Retrospective Data Collection
Demographics:
Demographic data such as age, sex, body mass index (BMI), the suspected causative factors for bronchiectasis and causes for exacerbation of the disease leading to RF were noted. Results of sputum specimen or bronchial tracheal aspirates obtained within 48 h following ICU admission were reviewed, and patients were classified into two groups depending on whether their culture findings were positive or negative for Pseudomonas aeruginosa.
Severity of Disease:
Criteria for assessing severity of the disease on ICU admission were collected: severity acute physiologic score (SAPS) II, presence of renal failure, results of arterial blood gases analysis, and presence of underweight.
Interventions and Outcomes:
Interventions and outcomes were recorded, lengths of ICU stay were recorded, and treatments and respiratory cares were considered for the entire stay in ICU. The outcome was survival at March 20, 2000. No patients were unavailable for follow-up.
Definitions:
In addition to the requirement of intubation before ICU admission, respiratory failure was considered when at least two of the following clinical signs or symptoms were noticed on ICU admission: cyanosis, dyspnea, impaired consciousness, and signs of respiratory muscle exhaustion in association with at least one of the following: PaO2 < 60 mm Hg while breathing room air, PaCO2 > 55 mm Hg, and/or pH < 7.30 while breathing room air or with supplemental oxygen. Renal failure was defined as serum creatinine level > 120 µmol/L (> 1.36 mg/100 mL). The presence of underweight was defined as body mass index (BMI) < 20 for male and 18.8 for female patients.10 Standard intensive care included oxygen therapy, chest physiotherapy, enteral nutrition, and antibiotics when required. Patients with hypercapnic respiratory failure despite intensive standard therapy were treated with assisted ventilation. When feasible, patients first received ventilation via a nasal or face mask in pressure-support mode. The patients with hemodynamic instability or impaired conscious were intubated, as were those unable to tolerate mask ventilation or those with gas exchange worsening despite NIV.
Statistical Analysis
Results are expressed as means ± SD. Subgroups for continuous variables were defined by dividing the whole groups according to median value. Patient survival was calculated from the data of ICU admission until death or March 1, 2000. Survival curves were generated by using Kaplan-Meier product limit method and were compared by the log-rank test. Univariate Cox regression was used to identify factors with potential prognostic significance. The Cox proportional hazards model was used to assess the independent contribution of each predictor with p < 0.1 in univariate Cox regression. Patients alive at the end of follow-up were censored. All comparisons were done with Statview 5 (SAS Institute; Cary, NC) statistical software package; p < 0.05 was considered significant.
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Results
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Sixty-seven adults with bronchiectasis were identified over the 9-year study period. Forty-eight patients were included in the analysis. Among the 19 patients who were not included in the study, 3 patients had a previous ICU stay for RF, 7 patients required ICU admission for a reason other than RF (acute renal failure, n = 2; hyponatremia and seizure, n = 2; liver transplantation, n = 1; meningitis, n = 2), 7 patients had chest radiographic and CT features of unilateral bronchiectasis, and 2 patients did not present RF criteria.
Mean age of the population at ICU admission was 63 ± 11 years (range, 35 to 88 years), and 28 patients (58%) were female. Sputum production was reported since childhood in 23 patients (48%). Bronchiectasis was considered idiopathic in 28 cases (58%) and believed to be postinfectious in 17 cases (35%). Rheumatoid arthritis was present in one case, humoral immunodeficiency (hyperimmunoglobinemia E syndrome) in one case, and 
1-antitrypsin deficiency in one case. Fourteen patients (25%) were treated with long-term oxygen therapy (LTOT), in association with long-term home nasal intermittent positive pressure ventilation (NIPPV) for 10 of them. CT scans demonstrated that four lobes or more were involved in 24 patients (50%), and that at least three lobes were involved for the other patients. Cylindrical bronchiectasis was the most common type (56%). Cystic type was noticed in 16 patients (33%), and varicose type was noticed in 5 patients (11%).
RF was associated with a disabling productive cough and/or an increase in purulent sputum production in 26 patients. For the others, the presumed provoking factors were pneumonia (n = 10), pneumothorax (n = 3), chest trauma (n = 1), hemoptysis (n = 2), heart failure (n = 4), and treatment with sedatives (n = 2). The status of the patients at ICU admission is reported in Table 1
. Thirteen patients (27%) were intubated before or within the first day following ICU admission. In 13 patients (27%), PaO2 while breathing room air was < 60 mm Hg. PaCO2 was > 55 mm Hg and/or pH < 7.30 while breathing room air or with supplemental oxygen in the 22 remaining patients (46%). Underweight was noticed in 15 patients (31%), renal failure in 8 patients (17%), and respiratory samples grew P aeruginosa in 20 patients (42%).
Risk Factors for Mortality in the ICU
During ICU stay, 9 patients (19%) were managed solely with standard intensive therapy, while NIV was used in 13 patients (27%) and intubation was required in 26 patients (54%). Nine patients (19%) died during the first stay in ICU; all of them had required intubation. ICU stays were 11 ± 9 days for survivors (range, 2 to 41 days) and 26 ± 40 days for nonsurvivors (range, 1 to 109 days). During the study period, ICU readmission was noted in 15 patients, among whom 4 patients (27%) died during their second ICU stay. Mean elapsed time from ICU discharge and ICU readmission was 419 ± 455 days (range, 14 to 1,282 days). During the study period, two patients had three ICU admissions, two patients had four admissions, and one patient had six admissions, all for RF.
Risk Factors for Mortality at 1 Year After the First ICU Stay
The median of follow-up was 1,244 days (range, 1 to 3,178 days; one patient died the day following ICU admission). Cumulative mortality was 19% (n = 9) in ICU and 40% (n = 19) at 1 year. Fifteen of the 29 deaths noted during the follow-up study occurred in the ICU. The cause of death was septic shock in 1 case, hemorrhagic shock due to digestive bleeding in 1 case, cardiac failure or myocardial infarction in 7 cases, and was considered as directly related to bronchiectasis and respiratory failure in 17 cases. The cause of death could not be ascertained in three patients. The results of univariate analysis are showed in Table 2
. Neither male gender nor underweight noticed on ICU admission differentiated patient outcomes after ICU discharge. Survival was not reduced for the patients with cystic bronchiectasis and those treated with long-term home NIPPV. The long-term prognosis was not poorer in the patients whose sputa grew P aeruginosa compared with those whose sputa did not grow P aeruginosa or grew organisms other than P aeruginosa. The results of the Cox proportional hazards analysis of factors associated with increased mortality after the first ICU admission for RF are shown in Table 3
. We included the subsequent dichotomous variables in multivariate analysis because they achieved a p value of 0.1: age (> 65 years vs 
65 years), cystic bronchiectasis (yes/no), SAPS II score (> 32 vs 32), presence of renal failure on ICU admission (yes/no), use of LTOT (yes/no), and intubation required (yes/no). Age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT admission (RR, 3.12; 95% CI, 1.47 to 6.40) were independently associated with reduced survival. The Kaplan-Meier estimates of survival for age > 65 years or 65 years, and LTOT before ICU (yes/no) are shown in Figure 1
. Comparisons by the log-rank tests were significant (age > 65 years, p = 0.008; LTOT, p = 0.042).
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Table 2. Results of Univariate Survival Analysis in 48 Patients With Bronchiectasis After the First ICU Admission for RF
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Table 3. Results of Cox Proportional Hazards Analysis of the Risk of Death After the First ICU Admission for RF Among 48 Patients With Bronchiectasis
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Figure 1. Kaplan-Meier curves showing survival rate of 48 patients with bronchiectasis after the first ICU admission for RF according to age on ICU admission (top, A) and use of LTOT before ICU admission (bottom, B).
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Discussion
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During the last decade, the literature focusing on the prognosis of bronchiectasis has been limited.11 Furthermore, patients with bronchiectasis are generally excluded from clinical studies performed in ICU12 because the mechanisms leading to RF appear particularly complex. As a result, data on short-term and long-term outcomes after an ICU stay are lacking for this disease.
We analyzed the survival of 48 patients with bilateral bronchiectasis after their first admission in ICU for RF. Nine patients (19%) died during their first ICU stay, and five patients died during the second ICU stay. The actuarial survival rate for the overall study population was 60% at 1 year. Age > 65 years and LTOT were the only factors recorded on ICU admission independently associated with a reduced survival in the multivariate survival analysis. To our knowledge, this is the first study focusing on long-term outcome of patients with bronchiectasis after the first ICU admission for RF. One could argue that some of the patients studied represent a subset of patients with COPD and some localized bronchial ectasia. However, each of the patients satisfied the CT description of bronchiectasis.5 In agreement with most previous studies, we found a predominance in female subjects,24 a specific cause was identified in 42% of the cases,13 and a predominance of cylindrical changes was noted on CT scans.6
The population studied was seen at an advance stage of the diseases, as evidenced by pulmonary function studies, the frequent use of LTOT, and the high rate of colonization or infection by P aeruginosa. Nevertheless, the mean age of patients at admission on ICU was higher than the reported mean age of death for bronchiectatic patients in the 1960s14 and 1970s.15 Our results suggest that the prognosis of patients with bronchiectasis patients has improved during the last 2 decades. This is in accordance with the results published by Säynäjäfangas et al,16 who reported a decreased number of hospital admissions due to complications of bronchiectasis in 1992 compared with 1977.
Long-term outcomes of patients with bronchiectasis have been compared to the outcome of COPD. Keistinen et al12 reviewed the National Hospital Discharge register in Finland and found that the prognosis of patients with bronchiectasis was better than patients with COPD who were matches according to age and sex. Chailleux et al17 noted that patients who required LTOT or prolonged home mechanical ventilation survived slightly longer when chronic RF was due to bronchiectasis than when it was due to COPD. Age > 65 years at ICU admission was associated with an increased long-term mortality in the present study. Advancing age has been also identified among the best predictors of short-term or long-term mortality after hospital admission for patients with COPD.1819 We found that SAPS > 32 on ICU admission was associated with a reduced survival in univariate analysis. To our knowledge, it is the first time that the accuracy of SAPS II has been assessed in a population formed exclusively by patients with bronchiectasis. Gender did not significantly influence outcomes, a result in accordance with those published by Pasteur et al,11 who demonstrated that lung damages in bronchiectasis progress at the same rate in both sexes. An interesting finding is the fact that survival of patients was not shorter when P aeruginosa was isolated from patient respiratory samples collected at the ICU admission. It has been demonstrated that patients with P aeruginosa colonization exhibit more extensive lung disease and have a more severe impairment of lung function,20 but not that P aeruginosa directly contributes to lung function decline.21 Similarly, we did not find that survival was reduced for patients with cystic bronchiectasis compared with those with cylindrical or varicose forms, whereas cystic bronchiectasis has been described as associated with sputum purulence and with growth of P aeruginosa.22 Poor nutritional status on ICU admission (assessed by a low BMI) was not associated with a reduced survival contrary to that reported for patients with COPD.10 However, BMI was probably overestimated in most patients because of the presence of edema related to right ventricular failure.
In addition to its retrospective nature, our study has several shortcomings. First, the relatively small number of patients limited our study. Second, because of the missing of recent spirometric data in six patients, the impact of lung function severity could not be evaluated here. Third, some factors that probably could be good predictors of reduced survival, such as the number of previous hospital admissions, indexes of quality of life, or pulmonary artery pressure at ICU admission, were not assessed. In addition, ICU admission criteria were not applied prospectively here, and indicators for ICU admission may have varied from one physician in charge to another. However, we do not believe that the fact that CT scans and chest radiographs were not reviewed by independent observers is a major limitation of our study.
Altered clearance of airway secretions, mucus impaction, and subsequent chronic infection are the main factors leading to respiratory failure both in bronchiectasis and in cystic fibrosis. Sood et al23 showed that ICU care was appropriate and effective for adults with cystic fibrosis. In their experience, NIV is helpful for these patients because it enables cough and facilitates clearance of secretions. Because we use home NIV in our patients with bronchiectasis and basal hypercapnia for several years,24 pressure support delivered via nasal or facial mask is actually the preferred respiratory support used in our ICU for RF in bronchiectasis (Table 4
). The fact that intubation requirement was associated with a reduced survival in univariate analysis suggests that NIV may be advantageous as has been demonstrated for patients suffering from exacerbations of COPD.25
In conclusion, we found that there was a 19% ICU mortality rate associated with the first episode of RF in patients with bilateral bronchiectasis. The mortality rate was 40% at 1 year, similar to the rate reported in patients with COPD after an ICU stay. By multivariate analysis, age > 65 years and use of LTOT were independent factors predicting reduced survival. To our knowledge, this is the first report providing information related to the impact of an ICU stay for RF on long-term outcome for patients with bronchiectasis.
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Footnotes
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Abbreviations: BMI = body mass index; CI = confidence interval; LTOT = long-term oxygen therapy; NIPPV = nasal intermittent positive pressure ventilation; NIV = noninvasive ventilation; RF = respiratory failure; RR = relative risk; SAPS = simplified acute physiology score
Received for publication February 11, 2003.
Accepted for publication November 4, 2003.
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Abstract
Introduction
