0
Original Research: BRONCHIECTASIS |

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis* FREE TO VIEW

Miguel Angel Martínez-García, MD; Juan-Jose Soler-Cataluña, MD; Miguel Perpiñá-Tordera, MD; Pilar Román-Sánchez, MD; Joan Soriano, MD
Author and Funding Information

*From the Pneumology Unit (Drs. Martínez-García and Soler-Cataluña) and Service of Internal Medicine (Dr. Román-Sánchez), Requena General Hospital, Valencia, Spain; Service of Pneumology (Dr. Perpiñá-Tordera), La Fe University Hospital, Valencia, Spain; and the Program of Epidemiology and Clinical Research (Dr. Soriano), Fundació Caubet-CIMERA, Illes Baleares, Mallorca, Spain.

Correspondence to: Miguel Angel Martínez-García, MD, Unidad de Neumología, Hospital General de Requena, Paraje Casa Blanca s/n, 43230, Valencia, Spain; e-mail: miangel@comv.es



Chest. 2007;132(5):1565-1572. doi:10.1378/chest.07-0490
Text Size: A A A
Published online

Background: Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis.

Methods: Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations.

Results: Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) [odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p = 0.005], more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p = 0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p = 0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline.

Conclusion: Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.

Figures in this Article

Bronchiectasis is a chronic airway disease that is characterized by abnormal destruction and dilation of the large airways, bronchi, and bronchioles.1As a result of the associated dysfunction of mucociliary clearance, a vicious circle is established involving persistent bacterial colonization, chronic inflammation of the bronchial mucosa, and progressive tissue destruction.2 Bronchiectasis is associated with chronic and frequently purulent expectoration, multiple exacerbations, and progressive dyspnea that can become disabling.13 These events gradually worsen the health-related quality of life of affected patients45.

Impaired lung function in patients with bronchiectasis usually leads to chronic airflow obstruction.2,45 Several factors have been previously associated with greater airflow obstruction in patients with bronchiectasis, including the pulmonary extension of the disease,67 greater thickening of the bronchial wall,8chronic colonization of the bronchial epithelium by Pseudomonas aeruginosa (PA),10 or high concentrations of proinflammatory markers in sputum or serum, such as neutrophilic elastase11or several adhesion molecules.12Nicotra et al13reported that adult nonsmoker patients with non-cystic fibrosis (CF) bronchiectasis had an accelerated loss of pulmonary function (FEV1) quantified as 54 mL per year, which is more than expected in the general population14 and is similar to the results of a loss of FEV1 of 49 mL per year published by King et al.15 To date, it is largely unknown which factors modify this loss and whether any management strategy slows this pulmonary decline. A limited number of studies are available, some suggesting that perhaps chronic colonization of the bronchial epithelium by PA,9 changes in the morphology of bronchiectasis, or the number of mucus plugs observed by high-resolution CT (HRCT) scanning might be correlated with a faster decline of FEV1 in these patients.,16To our knowledge, there has been no systematic assessment of other variables that might have a significant role in the natural history of patients with bronchiectasis, such as the number and severity of exacerbations, markers of systemic inflammation, or clinical correlates that have a demonstrated influence in other clinical conditions characterized by pulmonary function decline, namely, COPD1719 and CF.2021 We prospectively studied a cohort of adult patients with well-characterized non-CF bronchiectasis in a stable phase with the aim of observing changes in pulmonary function during a 24-month follow-up period and to identify factors associated with higher/lower pulmonary function decline in these patients.

Study Population

We studied all patients with bronchiectasis that had been diagnosed in our center (Hospital de Requena; Valencia, Spain), affecting more than one lung lobe, or with cystic bronchiectasis, unrelated to CF and in a clinically stable phase (ie, subjects had been free from acute exacerbation for at least 4 weeks prior to the start of the study). Exclusion criteria were as follows: current smokers; patients with a smoking history of > 10 pack-years; patients at occupational risk for COPD; patients with traction bronchiectasis due to severe emphysema or advanced fibrosis; patients with asthma as defined by the Global Initiative for Asthma guidelines22; or patients with other cardiopulmonary conditions other than bronchiectasis that could modify spirometry findings or the course of the disease. CF was excluded by two negative results of sweat tests conducted in those patients with bronchiectasis of unknown cause or with a clinical presentation compatible with CF.23 The study was approved by the local ethics committee, and all patients gave their informed consent to participate in the study.

Diagnosis of Bronchiectasis

The diagnosis of bronchiectasis was established in all cases by chest HRCT scanning in sections of 1 to 1.5 mm every 10 mm and subsequent reconstruction following the criteria described by Naidich et al.24HRCT scanning was performed a maximum of 24 months prior to the start of the study. To assess the presence and extension of bronchiectasis, the modified Bhalla score was used.25 The cause of bronchiectasis was established by our group protocol, which has been described elsewhere.5

From a posttuberculous origin, the past presence, along with bronchiectasis, of clear documented tuberculosis in a similar location in the presence of indirect HRCT scan findings of past tuberculosis (ie, apical fibrous tracts, calcified adenopathies, or granulomas) together with a positive Mantoux test was considered as an etiology of bronchiectasis, provided that bronchiectasis could not be explained by other causes and the clinical manifestations appeared after the tuberculous process. From a postinfectious origin, documented evidence of one or more nontuberculous pneumonic processes in the current location of bronchiectasis or the past presence of necrotizing pneumonia, provided onset of the clinical manifestations was posterior to the infectious process, was also considered as an etiology of bronchiectasis. This etiology was also considered in the presence of primary immune deficiencies, provided bronchiectasis could not be explained by other causes. The remaining diagnoses (eg, collagenosis, allergic bronchopulmonary aspergillosis, inflammatory diseases, ciliary dyskinesia, and other congenital disorders) were assessed according to clinician criteria, based on the required complementary test results. If no compatible etiologic diagnosis was established following all of the opportune complementary studies, bronchiectasis was classified as idiopathic.

Study Measurements
Baseline Data:

Baseline data were collected during the first study visit, between June and December 2003, in all patients who were in the stable phase. Collected data included general and anthropometric parameters, disease history, smoking history, and current treatments including long-acting β2-agonists, inhaled steroids (the dosage of inhaled steroids was expressed as beclomethasone units by using a conversion rate of 1 μg of beclomethasone dipropionate = 0.5 μg of fluticasone propionate, 1 μg of budesonide, or 2 μg of triamcinolone/flunisolide), systemic steroids, antibiotic therapy, inclusion in a physiotherapy program, and oxygen therapy. At the first study visit, the following tests were performed: collection of peripheral blood samples for measurement of erythrocyte sedimentation rate (ESR) in millimeters in the first hour, fibrinogen concentration (in milligrams per deciliter), and high-resolution C-reactive protein (CRP) [in milligrams per deciliter]; measurement of the mean amount of sputum produced daily (in milliliters) and collected according to a procedure published by our group elsewhere26; assessment of baseline dyspnea by the modified Medical Research Council scale27; and oxygen saturation (respiratory failure was defined by oxygen saturation of < 90%). One pair of sputum samples was collected in each of the 6 months prior to the first day of the study for microbiological testing, including Gram staining and culture in standard media, or special media in the event of a clinical suspicion of a specific microorganism. In valid sputum samples, chronic colonization by PA or another microorganism from sputum samples was considered when the microorganism appeared in concentrations of ≥ 105 CFU/mL in at least three sputum samples corresponding to different visits.28

Lung Function:

Full spirometry (V̇max Encore; SensorMedics; Yorba Linda, CA) was performed in all participants during the first study visit, in the morning between 8:00 am and 10:00 am, to determine FEV1 and FVC according to standard guidelines.29FEV1 and FVC were expressed as absolute values and as percent predicted values for the patient’s age, sex, and height.30 A minimum of three and a maximum of eight maneuvers were performed to obtain a coefficient of variation of < 5% in FEV1 relative to the best maneuver. Airflow obstruction was defined by an FEV1/FVC ratio of < 70%. Reversibility was tested by repeating spirometry 15 min after the inhalation of 400 μg of salbutamol.

Follow-up

Patients were invited to attend the clinic every 6 months for 2 years, to conduct a battery of tests (ie, full spirometry and microbiological analysis of six pairs of sputum samples collected within 6 months) and to report the number of bronchiectasis exacerbations. Participants were instructed to visit their family doctor in the event of respiratory symptom worsening. Participants were instructed to fill in a diary card with dates of medical consultations, symptoms, time to full recovery, and treatments, together with any primary care reports. This information was obtained directly by the investigators when patients were seen in the emergency department or were hospitalized. Exacerbation was defined as a persistent (> 24 h) deterioration of at least three respiratory symptoms (including cough, dyspnea, hemoptysis, increased sputum purulence or volume, and chest pain) with or without temperature, radiographic deterioration, systemic disturbances, or deterioration in chest signs.31 We defined as severe exacerbations of bronchiectasis those requiring treatment with systemic steroids, accompanied by respiratory failure, or requiring hospitalization. The need for systemic corticoid treatment or hospitalization was left to the discretion of the attending physician. Respiratory failure was defined as blood Po2 < 60 mm Hg. Finally, data were collected on all inhaled or systemic treatments during the study period.

Statistical Analysis

All data were tabulated as the mean and SE for quantitative variables, and as absolute values and percentages for qualitative variables. The normality of all variables was verified by the Kolmogorov-Smirnov test. In the absence of a normal distribution, nonparametric tests were used. The Student t test or Mann-Whitney U test was used for comparing two means, and the χ2 test as used for qualitative variables. For bivariate analysis, we stratified participants, using the cut point of the mean annual FEV1 decline, into two groups (rapid and nonrapid decliners). Variables with statistically significant differences in the bivariate analysis were included as independent variables in stepwise logistic regression analysis. The results were expressed as the odds ratio and 95% confidence interval for rapid decliners vs nonrapid decliners. To compare mean FEV1 variations with time, both within the group and between groups, we used analysis of variance repeated measurement analysis adjusting for age, gender, number of visits, and baseline FEV1. Any comparison with a p value < 0.05 was considered to be statistically significant.

Patients

Of 112 patients with bronchiectasis, who were never-smokers or had a smoking history of < 10 pack-years, we excluded 23 patients with suspected asthma, 5 patients with mental or physical impairments that prevented them from completing the study protocol, and 6 patients with unacceptable quality spirometry results. Two patients refused to participate in the study. The baseline characteristics of the 76 participants (48.7% men; mean age, 69.9 years; age range, 39 to 83 years) included in the study are reported in Table 1 . Of interest, 32.9% of participants had postinfectious bronchiectasis, 19.7% had posttuberculous bronchiectasis, and 42.1% had bronchiectasis of unknown etiology. Fifteen patients (19.7%) had chronic colonization by PA, and 14 (18.4%) by Haemophilus influenzae.

Follow-up

During the 2-year study, two patients died during the first 6 months and two were lost to follow-up. The remaining patients completed the study. The mean annual rate of exacerbations was 2.4 (SE, 0.28; range, 0 to 12), and the mean annual rate of severe exacerbations was 1.5 (SE, 0.23; range, 0 to 8). Of 15 patients with chronic colonization due to PA at the start of the study, 6 were treated with inhaled colistin, 7 were treated with oral quinolones (ciprofloxacin or levofloxacin), and two were treated with intermittent courses of IV ceftazidime. Despite treatment, only one patient had PA eradicated for > 6 months. During follow-up, there were no changes in bronchodilator or corticosteroid treatment except during exacerbations. Three patients required continuous treatment with oral corticosteroids (mean dose, 12.5 mg of prednisone).

Longitudinal Changes in FEV1 and Associated Factors

The mean annual decline in FEV1 was 52.7 mL, corresponding to −2.35% of the predicted percentage of FEV1 (Fig 1 ). This value was used as the cut-off point to stratify rapid decliners (n = 36; mean, −91.1 mL per year; SE, 21.1 mL per year) vs nonrapid decliners (n = 40; mean, −11.1 mL per year; SE, 28.1 mL per year). There were no significant differences in FEV1 decline between patients whether the bronchiectasis was postinfectious (n = 25; mean, −54.6 mL per year; SE, 27.4 mL per year), posttuberculous (n = 15; mean, −50.8 mL per year; SE, 26.1 mL per year), or idiopathic (n = 32; mean, −53.1 mL per year; SE, 22.3 mL per year). Rapid decliners were more frequently colonized by PA; produced more sputum volume per day; and had greater ESR and CRP, and more exacerbations (all p < 0.05). In a stepwise logistic regression analysis, independent factors associated with an accelerated decline in FEV1 were as follows: chronic sputum colonization by PA (p = 0.005); frequency of severe exacerbations (p = 0.014); and a high serum concentration of CRP as a marker of systemic inflammation (p = 0.023) [Table 2 ].

Figure 2 shows that patients with bronchiectasis who were chronically colonized by PA had a faster decline in annual FEV1 compared to those not colonized (−123.3 mL per year [-5.53%] vs −30.8 mL per year [–1.38%], respectively; p < 0.001). Similarly, patients with bronchiectasis experiencing ≥ 1.5 severe exacerbations per year had a faster decline in annual FEV1 compared to those experiencing < 1.5 exacerbations per year (−124.5 mL per year [–5.55%] vs −28.8 mL per year [–1.35%], respectively; p < 0.001) [Fig 3 ].

Our study, using a well-characterized cohort with stable, non-CF bronchiectasis, has shown for the first time that chronic sputum colonization with PA, more frequent severe exacerbations, and more systemic inflammation are independent factors associated with a faster decline of lung function. Regrettably, none of the long-term treatment strategies evaluated, including use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, or antibiotics had a lasting, significant effect on FEV1 decline.

The observed annual decline in FEV1 of 52.7 mL per year (−2.35% per year) mirrors the results reported by Nicotra et al13 in a group of 38 male and 85 female, adult, nonsmokers with non-CF bronchiectasis who showed an annual decline of 55 mL per year in FEV1. Similar results were observed by King et al,15 (–49 mL per year decline in FEV1) in a cohort of 101 nonsmoking bronchiectasis patients. All of these estimates are higher than those reported by Mannino and Davis,,14 of a decline in FEV1 of 39 mL per year (−1.43% per year) in individuals ≥ 65 years from the general population, and higher than those reported by Donaldson and colleagues,1718 in patients with severe COPD, averaging a decline in FEV1 of 36 to 40 mL per year.

The most important factor linked with an accelerated decline in FEV1 in this cohort of stable patients with non-CF bronchiectasis was chronic colonization with PA, associated with an FEV1 loss of 123.3 mL per year (−5.53% per year). This finding has already been reported in patients with CF-related bronchiectasis32 and non-CF-related bronchiectasis.9 A clear causal link between both cannot yet be established. A study by Evans et al9 suggested that chronic colonization by PA could identify the subgroup of patients whose lung function is already declining rapidly since PA selectively colonizes those persons with poor lung function. Davies et al33 have recently shown in patients with non-CF bronchiectasis that PA status is a marker of more severe airflow obstruction but is not associated with an accelerated decline in pulmonary function parameters. Our study does not confirm or refute the causal hypothesis postulated by Evans et al9 and Davies et al,33since in the course of the 2 years of follow-up we have not found patients with new colonization by PA that rules out any direct influence of the latter on the course of lung function. On the other hand, it must be underlined that the intensification of anti-PA antibiotic treatment in our patients (eg, with increased doses, longer treatment, or combined therapy) possibly could slow or even stop the impairment of lung function over the longer term. However, it is sensible to consider that patients colonized with PA experience more bronchial inflammation despite the multiple treatments aimed at eradicating it. We were only successful eradicating PA in 1 of 15 patients, although the pulmonary decline in FEV1 in this individual patient was still significant (103 mL per year), raising the possibility of an unsuccessful eradication or other alternatives. Taccetti et al34 have reported that eradicating PA was associated with a deceleration of pulmonary decline in CF patients. Nevertheless, in the present study we did not observe any significant differences in the loss of lung function between the bronchiectasis etiologies.

To our knowledge, our report of an association between the frequency of exacerbations and an accelerated decline in lung function is a novel finding. This association was reported in 2002 in COPD patients.17 However, Ellaffi et al35were unable to associate an accelerated lung function decline in CF patients with severe exacerbations that required hospitalizations. Some authors36have suggested that even in periods of clinical stability, patients with non-CF bronchiectasis experience increased bronchial inflammation. During an exacerbation, particularly an infective episode, large quantities of neutrophils migrate into the airway, which may lead to increased levels of proteolytic agents. These agents participate in the destruction of the lung matrix and contribute to the development of bronchiectasis. The same authors37 have noted that, while the observed increase in inflammation during exacerbations decreases with antibiotic treatment, it does not disappear entirely. This may be the cause of the greater functional deterioration observed in our patients with multiple severe exacerbations. It should be mentioned that we were very careful to collect data on all of the exacerbations in our patients during the study (ie, reports of symptoms by the patient, information provided by the primary care physician, or during direct care provided by the researchers if patients were admitted to the hospital). Nevertheless, the possibility that some of the least severe exacerbations were not detected and, therefore, were not recorded, and that they represent a bias in our results cannot be discarded entirely. We do not believe that the final conclusions would be altered in this case, however.

Although localized events appear to be active in patients with bronchiectasis, others36 have linked systemic inflammation with bronchiectasis, even in patients in a stable phase of the disease. Wilson et al38observed that, in an elevated percentage of patients with bronchiectasis not linked to a process of deterioration, there is a peripheral increase in the concentration of some acute-phase reactants such as CRP, ESR, or IgA that are correlated with some severity parameters, such as decreased pulmonary function or greater pulmonary disease extension in some cases, but not with respect to sputum microbiology. For this reason, some authors39 have proposed that systemic inflammation could be a spillover phenomenon of local inflammatory markers from the lungs, even though it is impossible to rule out distant production of inflammatory markers. Again, the association of lung function decline with systemic inflammation has been recently reported in COPD patients by Wilkinson et al.19 We consider our report of ESR, and especially CRP, together with lung function decline in bronchiectasis to be a novel finding. The association found in this study between peripheral levels of CRP and greater functional deterioration may be explained by the presence of systemic inflammation being related to more severe forms of disease, and that an increasing loss of pulmonary function is an indicator of bronchiectasis severity. In any case, the authors of this study are aware that both ESR and CRP are very nonspecific indicators of systemic inflammation, as their concentrations may be elevated by various diseases or in acute periods in the evolution of the bronchiectasis, despite careful testing in clinically stable situations. Nevertheless, to our knowledge, no specific, sensitive, systemic inflammatory indicator for bronchiectasis has been found. A note of interest is that none of the management strategies considered in our cohort, including therapy with long-acting β2-agonists, and inhaled and oral steroids, antibiotic courses, secretion clearance maneuvers, and oxygen therapy had a significant beneficial effect on lung function decline.

There are a number of limitations to the current study, which should be mentioned. First, the number of patients is limited, and they were recruited from a single hospital, which may be a limitation for the generalizability of the study results. Second, the follow-up period of 2 years is relatively short for precisely determining the mean annual decrease in FEV1. In any case, our results coincide with those of other studies with longer follow-up times. Therefore, the authors believe that larger, multicentric studies are needed, with longer follow-up periods and more patients, in order to corroborate our results.

To conclude, we have reported a decline in lung function (FEV1) that was estimated to be >50 mL per year in a well-characterized group of adult patients with non-CF bronchiectasis in stable phase and were followed up for 2 years. We have shown that chronic colonization of sputum by PA, frequency of severe exacerbations, and increased systemic inflammation are independently associated with a faster decline in FEV1.

Abbreviations: CF = cystic fibrosis; CRP = C-reactive protein; ESR = erithrocyte sedimentation rate; HRCT = high-resolution CT; PA = Pseudomonas aeruginosa

This study has been supported in part by a grant (Redrespira-ISCiii-RTIC-03/11) from the Spanish Ministry of Health.

Dr. Soriano was an employee of GlaxoSmithKline from 1998 to 2005 (see financial disclosure form). Drs. Martínez-García, Soler-Cataluña, Perpiña-Tordera, and Román-Sánchez have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Table Graphic Jump Location
Table 1. Demographic and Clinical Characteristics of all Participants (n = 76) and in Rapid vs Nonrapid Decliners*
* 

Values are given as the mean (SD) [range], unless otherwise indicated. Rapid Decliners = FEV1 decline of >52.7 mL/yr; Nonrapid Decliners = FEV1 decline of <52.7 mL/yr; Spo2 = oxihemoglobin saturation; BMI = body mass index; HI = Haemophilus influenzae; MRC = Medical Research Council; BMU = beclomethasone units; ICS = inhaled corticosteroid; NS = nonsignificant.

 

Comparison of rapid and nonrapid decliners.

Figure Jump LinkFigure 1. Mean (SD) decline in FEV1 adjusted by age, gender, time/number of measurements. The values in parentheses are percent predicted FEV1.Grahic Jump Location
Table Graphic Jump Location
Table 2. Multivariate Analysis of Factors Explaining Annual Percent Predicted FEV1 Decline After 2 Years of Follow-up in 76 Adult Patients With Bronchiectasis*
* 

OR = odds ratio; CI = confidence interval. Two patients died during the first 6 months of follow-up, and two other patients were lost to follow-up.

 

Stepwise logistic regression.

Figure Jump LinkFigure 2. Mean (SD) FEV1 according to PA colonization of the sputum adjusted by age, gender, time/number of measurements, and baseline FEV1 value. The values in parentheses are percent predicted FEV1.Grahic Jump Location
Figure Jump LinkFigure 3. Mean (SD) FEV1 according to the rate of severe exacerbations, adjusted by age, gender, time/number of measurements, and baseline FEV1 values. The values in parentheses are percent predicted FEV1.Grahic Jump Location
Cohen, M, Sahn, SA (1999) Bronchiectasis in systemic diseases.Chest116,1063-1074. [PubMed] [CrossRef]
 
Barker, AF Bronchiectasis.N Engl J Med2002;246,1383-1393
 
Ellis, DA, Thornley, PE, Wightman, AJ, et al Present outlook in bronchiectasis: clinical and social study and review of factors influencing prognosis.Thorax1981;36,659-664. [PubMed]
 
Wilson, CB, Jones, PW, O′Leary, CJ, et al Validation of the St. George′s Respiratory Questionnaire in bronchiectasis.Am J Respir Crit Care Med1997;156,536-541. [PubMed]
 
Martínez-García, MA, Perpiñá, M, Román, P, et al Determinants of quality of life in patients with clinically stable bronchiectasis.Chest2005;128,739-745. [PubMed]
 
Lynch, DA, Newell, J, Hale, V, et al Correlation of CT findings with clinical evaluation in 261 patients with symptomatic bronchiectasis.AJR Am J Roentgenol1999;173,53-58. [PubMed]
 
Koulouris, NG, Retsou, S, Kosmas, E, et al Tidal expiratory flow limitation, dyspnea and exercise capacity in patients with bilateral bronchiectasis.Eur Respir J2003;21,743-748. [PubMed]
 
Roberts, HR, Wells, AU, Milne, DG, et al Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function test.Thorax2000;55,198-204. [PubMed]
 
Evans, SA, Turner, SM, Bosch, BJ, et al Lung function in bronchiectasis: the influence ofPseudomonas aeruginosa.Eur Respir J1996;9,1601-1604. [PubMed]
 
Ho, PL, Chan, KN, Ip, MSM, et al The effect ofPseudomonas aeruginosainfection on clinical parameters in steady-state bronchiectasis.Chest1998;114,1594-1598. [PubMed]
 
Tsang, KW, Chan, KN, Ho, PL, et al Sputum elastase in steady-state bronchiectasis.Chest2000;117,420-426. [PubMed]
 
Zheng, L, Tipoe, G, Lam, WK, et al Up-regulation of circulating adhesion molecules in bronchiectasis.Eur Respir J2000;16,691-696. [PubMed]
 
Nicotra, MB, Rivera, M, Dale, AM, et al Clinical, pathophysiologic and microbiologic characterization of bronchiectasis in an aging cohort.Chest1995;108,955-956. [PubMed]
 
Mannino, DM, Davis, KJ Lung function decline and outcomes in an elderly population.Thorax2006;61,472-477. [PubMed]
 
King, PT, Holdsworth, SR, Freezer, NJ, et al Outcome in adult bronchiectasis.COPD2005;2,27-34. [PubMed]
 
Sheehan, RE, Wells, AU, Copley, SJ, et al A comparison of serial computed tomography and functional change in bronchiectasis.Eur Respir J2002;20,581-587. [PubMed]
 
Donaldson, GC, Seemungal, TAR, Bhowmik, A, et al Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.Thorax2002;57,847-852. [PubMed]
 
Donaldson, GC, Seemungal, TAR, Patel, IS, et al Airway and systemic inflammation and decline in lung function in patients with COPD.Chest2005;128,1995-2004. [PubMed]
 
Wilkinson, TMA, Donaldson, GC, Johnston, SL, et al Respiratory syncytial virus, airway inflammation, and FEV1decline in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med2006;173,871-876. [PubMed]
 
Hansen, CR, Pressler, T, Koch, C, et al Long-term azitromycin treatment of cystic fibrosis patients withPseudomonas aeruginosainfection: an observational cohort study.J Cyst Fibros2005;4,35-40. [PubMed]
 
Thornton, J, Elliott, R, Tully, MP, et al Long-term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis.Thorax2004;59,242-246. [PubMed]
 
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO workshop report; revised 2006. Available at: http://www.ginasthma.com/Guidelineitem.asp?|1=2&12=1&intId=60. Accessed October 10, 2007.
 
Warwick, WJ, Huang, NN, Waring, WW, et al Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chrolide sensor.Clin Chem1986;32,850-853. [PubMed]
 
Naidich, DP, McCauley, DI, Khouri, NF, et al Computed tomography of bronchiectasis.J Comput Assist Tomogr1982;6,437-444. [PubMed]
 
Bhalla, M, Turcios, N, Aponte, V, et al Cystic fibrosis: scoring system with thin-section CT.Radiology1991;179,783-788. [PubMed]
 
Martinez-García, MA, Perpiñá-Tordera, M, Román-Sánchez, P, et al Inhaled steroids improve quality of life in patients with steady-state bronchiectasis.Respir Med2006;100,1623-1632. [PubMed]
 
Mahler, DA, Weinberg, DM, Wells, CK, et al The measurement of dyspnea: contents, interobserver agreement and physiologic correlation of two new clinical indexes.Chest1984;85,751-758. [PubMed]
 
Canton, R, Cobos, N, de Gracia, J, et al Tratamiento antimicrobiano frente a la colonización pulmonar porPseudomonas aeruginosaen el paciente con fibrosis quística.Arch Bronconeumol2005;41(suppl),1-25
 
Casan, P, Burgos, F, Barberá, JA, et al. Recomendaciones de la Sociedad Española de Neumología y Cirugía Forácica (SEPAR): normativa para esprometría forzada. 1995; Ediciones Doyma. Barcelona, Spain:.
 
Roca, J, Sanchos, J, Agusti-Vidal, A, et al Spirometric reference values for a Mediterranean population.Bull Eur Physiopathol Respir1986;22,217-224. [PubMed]
 
Tsang, KW, Tan, KC, Ho, PL, et al Inhaled fluticasone in bronchiectasis: a 12 month study.Thorax2005;60,239-243. [PubMed]
 
Rosenbluth, DB, Wilson, K, Ferkol, T, et al Lung function decline in cystic fibrosis patients and timing for lung transplantation referral.Chest2004;126,412-419. [PubMed]
 
Davies, G, Wells, AU, Doffman, S, et al The effect ofPseudomonas aeruginosaon pulmonary function in patients with bronchiectasis.Eur Respir J2006;28,974-979. [PubMed]
 
Taccetti, G, Campana, S, Festini, F, et al Early eradication therapy againstPseudomonas aeruginosain cystic fibrosis patients.Eur Respir J2005;26,458-461. [PubMed]
 
Ellaffi, M, Vinsonneau, C, Coste, J, et al One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis.Am J Respir Crit Care Med2005;171,158-164. [PubMed]
 
Gaga, M, Bentley, AM, Humbert, M, et al Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis.Thorax1998;53,685-691. [PubMed]
 
Watt, AP, Brown, V, Courtney, J, et al Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis.Thorax2004;59,231-236. [PubMed]
 
Wilson, CB, Jones, PW, O′Leary, CJ, et al Systemic markers of inflammation in stable bronchiectasis.Eur Respir J1998;12,820-824. [PubMed]
 
Puren, AJ, Feldman, C, Savage, N, et al Patterns of cytokine expression in community-acquired pneumonia.Chest1995;107,1342-1349. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Mean (SD) decline in FEV1 adjusted by age, gender, time/number of measurements. The values in parentheses are percent predicted FEV1.Grahic Jump Location
Figure Jump LinkFigure 2. Mean (SD) FEV1 according to PA colonization of the sputum adjusted by age, gender, time/number of measurements, and baseline FEV1 value. The values in parentheses are percent predicted FEV1.Grahic Jump Location
Figure Jump LinkFigure 3. Mean (SD) FEV1 according to the rate of severe exacerbations, adjusted by age, gender, time/number of measurements, and baseline FEV1 values. The values in parentheses are percent predicted FEV1.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Demographic and Clinical Characteristics of all Participants (n = 76) and in Rapid vs Nonrapid Decliners*
* 

Values are given as the mean (SD) [range], unless otherwise indicated. Rapid Decliners = FEV1 decline of >52.7 mL/yr; Nonrapid Decliners = FEV1 decline of <52.7 mL/yr; Spo2 = oxihemoglobin saturation; BMI = body mass index; HI = Haemophilus influenzae; MRC = Medical Research Council; BMU = beclomethasone units; ICS = inhaled corticosteroid; NS = nonsignificant.

 

Comparison of rapid and nonrapid decliners.

Table Graphic Jump Location
Table 2. Multivariate Analysis of Factors Explaining Annual Percent Predicted FEV1 Decline After 2 Years of Follow-up in 76 Adult Patients With Bronchiectasis*
* 

OR = odds ratio; CI = confidence interval. Two patients died during the first 6 months of follow-up, and two other patients were lost to follow-up.

 

Stepwise logistic regression.

References

Cohen, M, Sahn, SA (1999) Bronchiectasis in systemic diseases.Chest116,1063-1074. [PubMed] [CrossRef]
 
Barker, AF Bronchiectasis.N Engl J Med2002;246,1383-1393
 
Ellis, DA, Thornley, PE, Wightman, AJ, et al Present outlook in bronchiectasis: clinical and social study and review of factors influencing prognosis.Thorax1981;36,659-664. [PubMed]
 
Wilson, CB, Jones, PW, O′Leary, CJ, et al Validation of the St. George′s Respiratory Questionnaire in bronchiectasis.Am J Respir Crit Care Med1997;156,536-541. [PubMed]
 
Martínez-García, MA, Perpiñá, M, Román, P, et al Determinants of quality of life in patients with clinically stable bronchiectasis.Chest2005;128,739-745. [PubMed]
 
Lynch, DA, Newell, J, Hale, V, et al Correlation of CT findings with clinical evaluation in 261 patients with symptomatic bronchiectasis.AJR Am J Roentgenol1999;173,53-58. [PubMed]
 
Koulouris, NG, Retsou, S, Kosmas, E, et al Tidal expiratory flow limitation, dyspnea and exercise capacity in patients with bilateral bronchiectasis.Eur Respir J2003;21,743-748. [PubMed]
 
Roberts, HR, Wells, AU, Milne, DG, et al Airflow obstruction in bronchiectasis: correlation between computed tomography features and pulmonary function test.Thorax2000;55,198-204. [PubMed]
 
Evans, SA, Turner, SM, Bosch, BJ, et al Lung function in bronchiectasis: the influence ofPseudomonas aeruginosa.Eur Respir J1996;9,1601-1604. [PubMed]
 
Ho, PL, Chan, KN, Ip, MSM, et al The effect ofPseudomonas aeruginosainfection on clinical parameters in steady-state bronchiectasis.Chest1998;114,1594-1598. [PubMed]
 
Tsang, KW, Chan, KN, Ho, PL, et al Sputum elastase in steady-state bronchiectasis.Chest2000;117,420-426. [PubMed]
 
Zheng, L, Tipoe, G, Lam, WK, et al Up-regulation of circulating adhesion molecules in bronchiectasis.Eur Respir J2000;16,691-696. [PubMed]
 
Nicotra, MB, Rivera, M, Dale, AM, et al Clinical, pathophysiologic and microbiologic characterization of bronchiectasis in an aging cohort.Chest1995;108,955-956. [PubMed]
 
Mannino, DM, Davis, KJ Lung function decline and outcomes in an elderly population.Thorax2006;61,472-477. [PubMed]
 
King, PT, Holdsworth, SR, Freezer, NJ, et al Outcome in adult bronchiectasis.COPD2005;2,27-34. [PubMed]
 
Sheehan, RE, Wells, AU, Copley, SJ, et al A comparison of serial computed tomography and functional change in bronchiectasis.Eur Respir J2002;20,581-587. [PubMed]
 
Donaldson, GC, Seemungal, TAR, Bhowmik, A, et al Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease.Thorax2002;57,847-852. [PubMed]
 
Donaldson, GC, Seemungal, TAR, Patel, IS, et al Airway and systemic inflammation and decline in lung function in patients with COPD.Chest2005;128,1995-2004. [PubMed]
 
Wilkinson, TMA, Donaldson, GC, Johnston, SL, et al Respiratory syncytial virus, airway inflammation, and FEV1decline in patients with chronic obstructive pulmonary disease.Am J Respir Crit Care Med2006;173,871-876. [PubMed]
 
Hansen, CR, Pressler, T, Koch, C, et al Long-term azitromycin treatment of cystic fibrosis patients withPseudomonas aeruginosainfection: an observational cohort study.J Cyst Fibros2005;4,35-40. [PubMed]
 
Thornton, J, Elliott, R, Tully, MP, et al Long-term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis.Thorax2004;59,242-246. [PubMed]
 
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO workshop report; revised 2006. Available at: http://www.ginasthma.com/Guidelineitem.asp?|1=2&12=1&intId=60. Accessed October 10, 2007.
 
Warwick, WJ, Huang, NN, Waring, WW, et al Evaluation of a cystic fibrosis screening system incorporating a miniature sweat stimulator and disposable chrolide sensor.Clin Chem1986;32,850-853. [PubMed]
 
Naidich, DP, McCauley, DI, Khouri, NF, et al Computed tomography of bronchiectasis.J Comput Assist Tomogr1982;6,437-444. [PubMed]
 
Bhalla, M, Turcios, N, Aponte, V, et al Cystic fibrosis: scoring system with thin-section CT.Radiology1991;179,783-788. [PubMed]
 
Martinez-García, MA, Perpiñá-Tordera, M, Román-Sánchez, P, et al Inhaled steroids improve quality of life in patients with steady-state bronchiectasis.Respir Med2006;100,1623-1632. [PubMed]
 
Mahler, DA, Weinberg, DM, Wells, CK, et al The measurement of dyspnea: contents, interobserver agreement and physiologic correlation of two new clinical indexes.Chest1984;85,751-758. [PubMed]
 
Canton, R, Cobos, N, de Gracia, J, et al Tratamiento antimicrobiano frente a la colonización pulmonar porPseudomonas aeruginosaen el paciente con fibrosis quística.Arch Bronconeumol2005;41(suppl),1-25
 
Casan, P, Burgos, F, Barberá, JA, et al. Recomendaciones de la Sociedad Española de Neumología y Cirugía Forácica (SEPAR): normativa para esprometría forzada. 1995; Ediciones Doyma. Barcelona, Spain:.
 
Roca, J, Sanchos, J, Agusti-Vidal, A, et al Spirometric reference values for a Mediterranean population.Bull Eur Physiopathol Respir1986;22,217-224. [PubMed]
 
Tsang, KW, Tan, KC, Ho, PL, et al Inhaled fluticasone in bronchiectasis: a 12 month study.Thorax2005;60,239-243. [PubMed]
 
Rosenbluth, DB, Wilson, K, Ferkol, T, et al Lung function decline in cystic fibrosis patients and timing for lung transplantation referral.Chest2004;126,412-419. [PubMed]
 
Davies, G, Wells, AU, Doffman, S, et al The effect ofPseudomonas aeruginosaon pulmonary function in patients with bronchiectasis.Eur Respir J2006;28,974-979. [PubMed]
 
Taccetti, G, Campana, S, Festini, F, et al Early eradication therapy againstPseudomonas aeruginosain cystic fibrosis patients.Eur Respir J2005;26,458-461. [PubMed]
 
Ellaffi, M, Vinsonneau, C, Coste, J, et al One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis.Am J Respir Crit Care Med2005;171,158-164. [PubMed]
 
Gaga, M, Bentley, AM, Humbert, M, et al Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis.Thorax1998;53,685-691. [PubMed]
 
Watt, AP, Brown, V, Courtney, J, et al Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis.Thorax2004;59,231-236. [PubMed]
 
Wilson, CB, Jones, PW, O′Leary, CJ, et al Systemic markers of inflammation in stable bronchiectasis.Eur Respir J1998;12,820-824. [PubMed]
 
Puren, AJ, Feldman, C, Savage, N, et al Patterns of cytokine expression in community-acquired pneumonia.Chest1995;107,1342-1349. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543