The impact of bronchiectasis in clinical presentation of asthma.
Methods: We evaluated 1680 asthmatics followed-up in our clinic. Fifty-one asthmatics had the diagnosis of bronchiectasis. These patients were compared with fifty-one age and gender matched asthmatics without bronchiectasis.
Results: The prevalence of bronchiectasis among the asthmatics was 3%. Asthma diagnosis was made at the age of 33.2 [+ or -] 16.8 years for asthmatics with bronchiectasis and 39.5 [+ or -] 16.2 years for pure asthmatics (P = 0.05). Asthmatics with bronchiectasis mostly had severe persistent asthma (49.0%), while pure asthmatics mostly had mild persistent and intermittent asthma (69.4%). History of hospitalization due to severe asthma exacerbation and presence of chronic respiratory failure was significantly higher in bronchiectatic group.
Conclusions: These data show that bronchiectasis can contribute to severe and difficult to control asthma with pulmonary complications like chronic respiratory failure.
Key Words: asthma, bronchiectasis, asthma severity, asthma control
Though asthma and bronchiectasis are two different diseases in pathophysiology, natural history, and prognosis and management, they are both defined as members of the family of chronic obstructive pulmonary disease. (1,2) Even though bronchiectasis is characterized by dilation of airways rather than narrowing, the coexistence of asthma and bronchiectasis has been shown in many patients. Whether asthma or atopy have a causative role in the pathogenesis of bronchiectasis or vice versa has been widely discussed in various reports. (3-8) However, none of the reports investigated the impact of coexisting bronchiectasis on asthma. So the aim of this study was to evaluate the clinical features of asthmatics with bronchiectasis compared with pure asthmatics.
Materials and Methods
Medical records of 1680 asthma cases admitted to our clinic between 1996 and 2003 were reviewed retrospectively. Asthma diagnosis was made according to the current Global Initiative for Asthma (GINA) recommendations at the time of the diagnosis. (9,10) Among these cases, 51 asthmatics were determined to have the diagnosis of bronchiectasis before or after the diagnosis of asthma during their follow-up in our outpatient clinic. Diagnosis of bronchiectasis was made by high resolution computed tomography (HRCT) of the thorax (HiSpeed CT/I, GE Medical Systems, Milwaukee, WI) according to the criteria described by McGuinness et al. (11) HRCT was planned by the pulmonologists in charge of the outpatient clinic in the presence of findings consistent with bronchiectasis on chest x-ray (CXR) and/or consistent clinical features.
For the control group, 51 age- and gender-matched asthmatics with normal chest x-ray were randomly selected from the 1680 patients' case data after excluding the 51 bronchiectatics.
The clinical features of these patients were evaluated and compared. Asthma severity was assessed according to the GINA guideline, (9,10) based on the symptoms and the pulmonary function tests obtained when the patients were clinically stable and had been free from acute respiratory infections for at least two months.
Patients were classified as having chronic respiratory failure if they had Pa[O.sub.2] at or below 55mmHg or Sa[O.sub.2] at or below 88%, with or without hypercapnia on spontaneous breathing, in room air, when the patients were clinically stable and had been free from acute respiratory infections for at least two months.
Spirometric parameters were measured with a spirometer (Vmax 20 Pulmonary Spirometry Instrument, Sensor Medics Corp., Yorba Linda, CA, US). Spirometer was calibrated once every testing day by a three liter volume syringe according to the recommendations of the manufacturer. Three expiratory maneuvers were measured per patient, and the best value was expressed as a percentage of the predicted value and as an absolute value. Bronchodilator response was assessed as > 12% improvement in [FEV.sub.1] after inhalation of 200 [micro]g salbutamol.
Atopy was assessed by skin prick tests to 13 common allergens (Dermatophagoides farinae, D. pteronyssinus, Cladosporium, Aspergillus mix, cat fur, dog hair, grasses, Corylus avellana, Populus alba, Olea europaea, cereals, positive histamine control and negative saline control) (Stallergens SA, France). The study subjects were characterized as atopic if they had a positive cutaneous reaction with a [greater than or equal to]3 mm skin wheal response. (12)
Statistical analysis was performed with SPSS for windows, version 10.0.1 (SPSS, Chicago, IL). Values were expressed as mean [+ or -] SD. Continuous variables were compared with Student's t test. The chi-square or Fisher's exact test was used to compare categorical variables. All p values were two-tailed, and a p of <0.05 was considered statistically significant.
Within the 8 year period that we reviewed, 3% of asthmatic patients were found to have bronchiectasis. The study groups were well matched for age and sex (Table 1). Asthma diagnosis was made at the age of 33.2 [+ or -] 16.8 (median: 33) and 39.5 [+ or -] 16.2 (median: 38) years in asthmatics with bronchiectasis and pure asthmatics, respectively (P = 0.05). Demographic and asthma related variables of the two study groups are summarized in Table 1. Pulmonary function was found to be significantly worse in asthmatics with bronchiectasis (Table 2). According to the GINA guideline's assessment of the severity of disease, (9,10) 3.9% of the asthmatics with bronchiectasis had mild intermittent asthma, 23.5% had mild persistent asthma, 23.5% had moderate persistent asthma and 49.0% had severe asthma. These rates were 32.7%, 36.7%, 22.4% and 8.2% for pure asthmatics (P > 0.001, for mild intermittent and severe asthmatics in two groups).
The major pulmonary symptom was dyspnea in both groups (86.3% and 70.6% in asthmatics with bronchiectasis and pure asthmatics, respectively) followed by cough (11.8% and 29.4% in asthmatics with bronchiectasis and pure asthmatics, respectively). Only one patient in the bronchiectatic group had sputum as a major symptom. However, 72.5% of the asthmatics with bronchiectasis had sputum complaints while only 35.3% of the pure asthmatics had sputum complaints (P < 0.001). History of hemoptysis (at least once) was present in 21.6% of the asthmatics with bronchiectasis versus none of the pure asthmatics (P < 0.001).
None of the asthmatics with bronchiectasis had a diagnosis of allergic bronchopulmonary aspergillosis or cystic fibrosis, and none of the patients in either group was steroid dependent.
Radiologically, bronchiectasis was unilateral in 25 patients (49%) and bilateral in the remaining 26 of the asthmatics with bronchiectasis. The most affected lobes were the lower lobes (43%). The cause of bronchiectasis was previous pulmonary tuberculosis in 6, pneumonia in childhood in 10 and unknown in 35 patients. Asthma was diagnosed before bronchiectasis in 34 patients (66.7%).
These data show that bronchiectasis can contribute to severe asthma with respiratory complications like chronic respiratory failure. These patients are also at a higher risk for severe asthma attack leading to hospitalization.
Although previous reports indicated that asthma tends to manifest itself after bronchiectasis, (8) in our study we found that 66.7% of the patients had asthma diagnosis before bronchiectasis. This finding can be discussed in two different ways. First, it may be interpreted as a support for the idea that asthma can lead to bronchiectasis. (3,7,13-15) Second, it may indicate that the clinical signs of bronchiectasis are overlooked in patients with similar pulmonary symptoms like asthma.
The interaction between asthma and bronchiectasis has been analyzed in various studies. The hypothesis that asthma and atopy may have a role in the pathogenesis of bronchiectasis was first postulated in 1939. (13) The role of early childhood asthmatic factors in bronchiectasis pathogenesis was emphasized later. (3) Since 1939 there have been many studies reporting positive relationships between bronchiectasis and bronchial hyperreactivity and/or asthma. (3,5-8,16-18) While some studies proposed that this was because of a direct link between bronchiectasis and asthma/atopy, others could not find any relationship between bronchiectasis and atopy. (4,5) Hence, the question of which condition predisposes to the other is still debatable. In our study, though, asthmatics with bronchiectasis were younger than the pure asthmatics at the time of asthma diagnosis; the median age asthma diagnosis made was 33 years in asthmatics with bronchiectasis. Only 10 of 51 patients were under 18 years at the time of asthma diagnosis, which excludes the effects of childhood asthma on bronchiectasis. Moreover, there were no significant differences in the prevalence of atopy among the two study groups.
In our opinion, the second idea is more likely. Clinical symptoms of these two diseases may overlap significantly as symptoms of cough, sputum and dyspnea can occur in either asthma or bronchiectasis alone. (7)
The reported prevalence of asthma in patients with bronchiectasis ranges from 2.7% to 42.0% in different series. (3,5,6,17) Prevalence of bronchiectasis in asthma was reported only from Finland in 1997. Our bronchiectasis rate was similar with this study, which reported a bronchiectasis prevalence of 1.8% among new asthma cases. (8) It was not surprising to see that nearly half of our patients had unilateral bronchiectasis. The most common etiology reported for localized disease is infection-related bronchial damage. Previous mycobacterial disease is still the leading cause for infection related bronchiectasis in adults, and this condition is not uncommon in our country. (19)
In the large asthma community surveys, more patients are classified as having mild intermittent and mild persistent asthma (range 56%-61.9%) than severe persistent asthma (range 8.7%-19.1%). (20-22) An important finding of this study is that in the pure asthmatic group, asthma severity rates are consistent with the large community surveys, while most of the asthmatics with bronchiectasis (49%) were classified as severe persistent asthma.
We have shown that nearly half of the asthmatics with bronchiectasis had a history of visits to the emergency room leading to hospitalization due to severe asthmatic attack. According to the definition of asthma control in the GINA guideline, (10) this data leads us to a conclusion that a significantly higher proportion of the asthmatics with bronchiectasis were poorly controlled when compared with pure asthmatics. Moreover, chronic respiratory failure rate (a severe complication of chronic respiratory diseases) was significantly higher in the bronchiectatic group. The duration of asthma was longer in asthmatics with bronchiectasis; however, we cannot propose that this has any relation with asthma control.
One limitation of this study was its retrospective design, which can lead to a selection bias. A prospective screening study with HRCT in newly diagnosed asthmatics would have stronger results. However, it will not be ethical and cost-effective to have a HRCT scan in such a high number of asthmatics.
Concerning all these results, we emphasize that bronchiectasis can contribute to severe and difficult to control asthma with pulmonary complications like chronic respiratory failure. However, from the clinical point of view, we conclude that it is important to recognize the two diseases separately and treat them accordingly.
1. Panettieri RA, Fishman AP. Chronic obstructive pulmonary disease: overview. In: Fishman's Manuel of Pulmonary Diseases and Disorders; Fishman AP, Elias JA, Fishman JA, Grippi MA, Kaiser LR, Senior RM, Eds. Philadelphia, McGraw-Hill, 2002, pp 105-117.
2. Mysliwiec V, Pina JS. Bronchiectasis: the 'other' obstructive lung disease. Postgrad Med 1999;106:123-131.
3. Varpella E, Laitinen LA, Keskinen H, et al. Asthma, allergy and bronchial hyper-reactivity to histamine in patients with bronchiectasis. Clin Allergy 1978;8:273-280.
4. Murphy MB, Reen DJ, Fitzgerald MX. Atopy, immunological changes, and respiratory function in bronchiectasis. Thorax 1984;39:179-184.
5. Pang J, Chan HS, Sung JY. Prevalence of asthma, atopy, and bronchial hyperreactivity in bronchiectasis: a controlled study. Thorax 1989;44:948-951.
6. Ip M, Lam WK, So SY, et al. Analysis of factors associated with bronchial hyperreactivity to methacholine in bronchiectasis. Lung 1991;169:43-51.
7. Ip MSM, So SY, Lam WK, et al. High prevalence of asthma patients with bronchiectasis in Hong Kong. Eur Respir J 1992;5:418-423.
8. Saynajakangas O, Keistinen T, Tuuponen T, et al. Links between hospital diagnosis of bronchiectasis and asthma. Allergy 1997;52:1120-1122.
9. Global initiative for asthma (GINA). Global strategy for Asthma management and prevention. NHLBI/WHO workshop report. National Institute of Health. National heart, Lung and Blood institute. January 1995. NIH Publication No: 95-3659.
10. Global initiative for asthma (GINA). Global strategy for Asthma management and prevention. NHLBI/WHO workshop report. National Institute of Health. National heart, Lung and Blood institute. Revised 2002. NIH Publication No: 02-5639.
11. McGuinness G, Naidich DP, Leitman BS, et al. Bronchiectasis: CT evaluation. AJR Am J Roentgenol 1993;160:253-259.
12. Slavin RG. Diagnostic tests in allergy. In: Fireman P, Slavin RG (eds). Atlas of Allergies. 2nd ed. London, Mosby-Wolfe, 1996, pp 43-56.
13. Watson S, Kibler C. The role of allergy in bronchiectasis. J Allergy 1939;10:364-369.
14. Robinson AE, Campbell JB. Bronchography in childhood asthma. Am J Radiol 1972;116:559-566.
15. Ostergaard PA. A prospective study on non-Ig E mediated asthma in children. Acta Paediatr Scand 1988;77:112-117.
16. Holmgren A, Ripe E. Airway conductance after inhalation of microaerosols of histamine chloride in healthy subjects and in patients with bronchiectasis before and after operation. Scand J Respir Dis 1973;54:215-222.
17. Bahous J, Cartier A, Pineau L, et al. Pulmonary function tests and airway responsiveness to methacholine in chronic bronchiectasis of the adult. Bull Eur Physiopathol Respir 1984;20:375-380.
18. Yorgancioglu A, Sakar A, Tarhan S, et al. High resolution computed tomography findings in patients with asthma. Tuberk Toraks 2003;51:5-10.
19. O'Regan AW, Berman JS. Bronchiectasis. In: Crapo JD, Glassroth J, Karlinsky J, King TE Jr (eds). Baum's Textbook of Pulmonary Diseases. 7th edition. Philadelphia, Lippincott Williams & Wilkins, 2004, pp 257-278.
20. Asthma in America Survey Slide Kit, Slide 20 [Asthma in America[IM] Survey Project web site]. Available at: http://www.asthmainamerica.com/slides/slide20.htm. Accessed March 1, 2007.
21. Rabe KF, Vermeire PA, Soriano JB, et al. Clinical management of asthma: the asthma insights and reality in Europe (AIRE) study. Eur Respir J 2000;16:802-807.
22. Verleden GM, De Vuyst P. Assessment of asthma severity and treatment by GPs in Belgium: an Asthma Drug Utilization Research Study (ADUR). Respir Med 2002;96:170-177.
A nation of sheep will beget a government of wolves. --Edward R. Murrow
I. Kivilcim Oguzulgen, MD, Firdevs Kervan, MD, Turkan Ozis, MD, and Haluk Turktas, MD
From Gazi University School of Medicine, Department of Pulmonary Medicine, Ankara, Turkey.
Reprint requests to Dr. I. Kivilcim Oguzulgen, Gazi University School of Medicine, Department of Pulmonary Medicine, Turan Gunes Bulvari 92/2, 06550, Cankaya, Ankara, Turkey. Email: firstname.lastname@example.org
Accepted October 20, 2006.
RELATED ARTICLE: Key Points
* Bronchiectasis can contribute to severe and difficult to control asthma.
* Asthmatic patients with bronchiectasis have a higher risk for severe asthma attack leading to hospitalization.
* Bronchiectasis can contribute to severe pulmonary complications in asthmatics like chronic respiratory failure.
* It is important to recognize bronchiectasis in asthmatics and treat them accordingly.
Table 1. Demographic and asthma related variables of the patients Asthmatics with bronchiectatics Pure asthmatics (n = 51) (n = 51) P Age (years) 51.5 [+ or -] 14.5 51.6 [+ or -] 14.5 NS Gender (F/M) 36/15 36/15 NS Duration of asthma 18.8 [+ or -] 14.3 12.2 [+ or -] 12.2 0.014 (years) Smoking history: Never smoker 70.6% 62.7% NS Exsmoker 27.4% 2% 0.000 Current smoker 2% 35.3% 0.000 Presence of Atopy 15.7% 25.5% NS History of 49% 17.6% 0.001 hospitalization due to severe asthma exacerbation Presence of chronic 9.8% 0 0.05 respiratory failure (with the indication of long-term oxygen therapy) NS, not significant. Table 2. Pulmonary function tests of the study population Asthmatics with bronchiectatics Pure asthmatics (n = 51) (n = 51) P [FEV.sub.1] (%) 62.7 [+ or -] 22.6 89.1 [+ or -] 18.1 0.000 FVC (%) 78.8 [+ or -] 19.8 99.4 [+ or -] 16.9 0.000 [FEV.sub.1]/FVC % 66.8 [+ or -] 12.6 76.6 [+ or -] 11.7 0.000 Bronchodilator response 19.0 [+ or -] 14.5 22.5 [+ or -] 17.8 NS in [FEV.sub.1] (%) NS, not significant.