Bronchiectasis

Bronchiectasis...brief note on introduction, types, clinical features and management

1. Bronchiectasis Pratap Sagar Tiwari , MD, Internal Medicine Note: This is a lecture class slide for MBBS students

2. Introduction Bronchiectasis :defined by the presence of permanent and abnormal dilation of the bronchi. [1,2] Bronchiectasis is an uncommon disease, most often secondary to an infectious process , that results in the abnormal and permanent distortion of one or more of the conducting bronchi or airways. Bronchiectasis shares many clinical features with COPD, including inflamed and easily collapsible airways, obstruction to airflow, and frequent office visits and hospitalizations. The diagnosis is usually established clinically on the basis of chronic daily cough with viscid sputum production , and radiographically by the presence of bronchial wall thickening and luminal dilatation on chest CT scans [  3]. Barker AF. Bronchiectasis. N Engl J Med. 2002;346:1383–1393. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med. 2006;100:2183–2189. Barker AF. Bronchiectasis. N Engl J Med 2002; 346:1383.

3. Types In 1950, Reid categorized bronchiectasis as having three main phenotypes:[1] 1) tubular(cylindrical) :characterized by smooth dilation of the bronchi; 2) varicose (bulbous):in which the bronchi are dilated with multiple indentations; 3) cystic (saccular/balloon appearance):in which dilated bronchi terminate in blind ending sacs. Whitwell classified bronchiectasis into three different types: Follicular, Saccular, and Atelectatic . Follicular bronchiectasis was the dominant form and this corresponded to tubular bronchiectasis (the main form commonly seen). Bronchiectasis has been described as being localized ( ie , confined to one lobe) or generalized. Most commonly it is generalized and seems to be most common in the lower lobes.[2,3] The involvement of the lower lobes may reflect gravity dependent retention of infected secretions. Reid LM. Reduction in bronchial subdivision in bronchiectasis. Thorax. 1950 Sep. 5(3):233-47. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med. 2006;100:2183–2189. Field E. Bronchiectasis: a long-term follow-up of medical and surgical cases from childhood. Arch Dis Child. 1961;36:587–603. Can also be differentiated as : Congenital & Acquired or Cystic fibrosis associated and Non CF Bronchiectasis. If Associated with Post fibrosis: Traction Bronchiectasis Without Must expectorant: Dry Bronchiectasis

4. Illustration: Follicular Bronchiectasis

5. Cole’s “vicious cycle hypothesis”[1] Cole proposed that an environmental insult often on a background of genetic susceptibility (impaired mucociliary clearance) resulting in persistence of microbes in the sinobronchial tree and microbial colonization. The microbial infection caused chronic inflammation resulting in tissue damage and impaired mucociliary motility. In turn this led to more infection with a cycle of progressive inflammation causing lung damage. The current view is that the two factors required for the development of this condition are persistent infection and a defect in host defense . Cole PJ. Inflammation: a two-edged sword – the model of bronchiectasis. Eur J Respir Dis Suppl . 1986;147:6–15.

6. Path…. continue The dominant cell types involved in the inflammatory process in bronchiectasis are neutrophils, lymphocytes, and macrophages .[1] Neutrophils are the most prominent cell type in the bronchial lumen [2], and release mediators , particularly proteases/elastase which cause bronchial dilation ( ie , bronchiectasis).[3] The infiltrate in the cell wall is predominantly composed of macrophages and lymphocytes .[2] Studies have reported that the main lymphocyte is the T cell [4] and these are cells that are likely to produce the lymphoid follicles described by Whitwell. Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J. 2008;31:396–406. Eller J, Lapa e Silva JR, Poulter LW, Lode H, Cole PJ. Cells and cytokines in chronic bronchial infection. Ann N Y Acad Sci. 1994;725:331–345. Khair OA, Davies RJ, Devalia JL. Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. Eur Respir J. 1996;9:1913–1922. Lapa e Silva JR, Guerreiro D, Noble B, Poulter LW, Cole PJ. Immunopathology of experimental bronchiectasis. Am J Respir Cell Mol Biol. 1989;1:297–304.

7. Etiologic/risk factors associated with bronchiectasis Postinfective ( postpneumonia , whooping cough, measles, mycobacterial infection ) Mucociliary disorder (immotile cilia, Kartagener’s syndrome, Young’s syndrome ) Obstructive (foreign body, mycobacterial infection, obstructing cancer) Immune disorder ( hypogammaglobulinemia , HIV infection, cancer, allergic bronchopulmonary aspergillosis, transplant rejection) Rheumatic/inflammatory disease (rheumatoid arthritis, inflammatory bowel disease) Extremes of age Malnutrition/socioeconomic disadvantage Chronic obstructive pulmonary disease Aspiration Alpha1-antitrypsin deficiency Miscellaneous (yellow nail syndrome)

8. Etiologic factors: Post infectious The most common cause of bronchiectasis is the literature is post infectious. A possible mechanism for post infectious bronchiectasis is a significant infection in early childhood which causes structural damage to the developing lung and permits bacterial infection which is over time persistent infection may then result in bronchiectasis.

9. Etiologic factors: Post infectious…. continue One well characterized form of bronchiectasis occurs in the context of mycobacterial infection and this form is particularly prevalent in the right middle lobe with nontuberculous mycobacterium.[ 1,2,3] The mechanism of this form of bronchiectasis appears to arise from lymph node obstruction. The acute infection causes enlargement of peribronchial nodes which obstruct the bronchus and result in secondary bronchiectasis. This bronchial dilation persists when the mycobacterial infection resolves and the nodes return to normal size. Whitwell F. A study of the pathology and pathogenesis of bronchiectasis. Thorax. 1952;7:213–219. Lynch DA, Simone PM, Fox MA, Bucher BL, Heinig MJ. CT features of pulmonary Mycobacterium avium complex infection. J Comput Assist Tomogr . 1995;19:353–360. Fujita J. Radiological findings of non-tuberculous mycobacteria respiratory infection. Kekkaku . 2003;78:557–561.

10. Etiologic factors: Muco -ciliary clearance Muco -ciliary clearance is a key defence mechanism against pulmonary infection. Its compromise is important in the development of the vicious cycle of bronchiectasis as proposed by Cole.[1] Cystic fibrosis is associated with defective muco -ciliary clearance . The most prominent cilial disorder is primary ciliary dyskinesia (PCD) which combines upper and lower respiratory tract infection, male infertility and in approximately 50%, situs inversus . PCD arises primarily from a defect in the dynein arms which are necessary for normal cilial beating. [2] Bronchiectasis is a prominent manifestation of PCD. Young’s syndrome is another condition in which the primary defect is thought to be defective mucous function.[3] Cole PJ. Inflammation: a two-edged sword – the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6–15. Omran H, Kobayashi D, Olbrich H, et al. Ktu /PF13 is required for cytoplasmic pre-assembly of axonemal dyneins . Nature. 2008;456: 611–616. Friedman KJ, Teichtahl H, De Kretser DM, et al. Screening Young syndrome patients for CFTR mutations. Am J Respir Crit Care Med. 1995;152:1353–1357.

11. Chronic obstructive pulmonary disease There is also some overlap in the pathology of COPD and bronchiectasis. Both conditions have neutrophils and T lymphocytes as the predominant inflammatory cell,[1,2] protease release causes pulmonary damage and lymphoid follicles have a role in airflow obstruction.[3,4] Fuschillo S, De Felice A, Balzano G. Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms. Eur Respir J. 2008;31:396–406. Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343:269–280. Whitwell F. A study of the pathology and pathogenesis of bronchiectasis. Thorax. 1952;7:213–219. Hogg JC, Chu F, Utokaparch S, et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:2645–2653.

12. Etiologic factors: Rheumatological /inflammatory conditions There is a well described association between bronchiectasis and rheumatoid arthritis. In rheumatoid arthritis the incidence of bronchiectasis has been described to be 1%–3%. Recent studies of patients with RA have described the prevalence of bronchiectasis on HRCT in such patients as being up to 30%.[1] Bronchiectasis may also occur in association with Sjogren’s syndrome63 and Churg –Strauss syndrome.[2] It is possible that immune suppression may predispose to chronic airway infection.[3] Bronchiectasis also occurs in subjects with inflammatory bowel disease.[4] Cortet B, Flipo RM, Remy- Jardin M, et al. Use of high resolution computed tomography of the lungs in patients with rheumatoid arthritis.Ann Rheum Dis. 1995;54:815–819. Larche MJ. A short review of the pathogenesis of Sjogren’s syndrome. Autoimmun Rev. 2006;5:132–135. King P. Churgh -Strauss syndrome and bronchiectasis. Respir Med Extra.2007;3:26–28. Black H, Mendoza M, Murin S. Thoracic manifestations of inflammatory bowel disease. Chest. 2007;131:524–532.

13. Etiologic factors: Alpha1-antitrypsin deficiency Alpha1-antitrypsin deficiency is associated with increased risk of COPD and bronchiectasis. Parr and colleagues studied the prevalence of airways disease in AAT deficient subjects and found that 70 of 74 subjects had radiological evidence of bronchiectasis and 20 subjects were classified as having clinically significant bronchiectasis.[1] Parr DG, Guest PG, Reynolds JH, Dowson LJ, Stockley RA. Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2007;176:1215–1221.

14. Microbiology A large number of different pathogens have been isolated in studies of microbiologic flora in bronchiectasis. The main findings from recent studies have been that Haemophilus influenza is the most common pathogen (range 29%–70%) followed by Pseudomonas aeruginosa (range 12%–31%).[1,2] and others include Moxarella . The role of viral infection in bronchiectasis is not well defined . Becroft [3] identified adenovirus as a risk factor for the development of bronchiectasis in young children. Viral infections have a role in exacerbations of COPD but this has not been defined for bronchiectasis .[4] Nicotra MB, Rivera M, Dale AM, Shepherd R, Carter R. Clinical, pathophysiologic, and microbiologic characterization of bronchiectasis in an aging cohort. Chest. 1995;108:955–961. Pasteur MC, Helliwell SM, Houghton SJ, et al. An investigation into causative factors in patients with bronchiectasis. Am J Respir Crit Care Med. 2000;162:1277–1284. Becroft DM. Bronchiolitis obliterans, bronchiectasis, and other sequelae of adenovirus type 21 infection in young children. J Clin Pathol . 1971;24:72–82. Seemungal T, Harper-Owen R, Bhowmik A, et al. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med.2001;164:1618–1623.

15. Cigarette smoking A causal role for cigarette smoking in bronchiectasis has not been demonstrated conclusively. However, smoking and repeated infections may worsen pulmonary function and accelerate the progression of disease that is already present [  1  ]. Popa V. Airway obstruction in adults with recurrent respiratory infections and IgG deficiency. Chest 1994; 105:1066.

16. Clinical manifestations The classic clinical manifestations of bronchiectasis are cough and the daily production of mucopurulent and tenacious sputum lasting months to years. The older literature also described " dry bronchiectasis " with episodic hemoptysis and no sputum production , but this presentation is less common. Other, less specific complaints include dyspnea, wheezing, and pleuritic chest pain. There is generally a past history of repeated respiratory tract infections over several years, although a single episode of severe bacterial pneumonia, pertussis, tuberculosis, and Mycoplasma infection can also result in bronchiectasis.

17. DIAGNOSIS The purpose of a diagnostic evaluation is radiographic confirmation of the diagnosis, identification of potentially treatable causes, and functional assessment The evaluation consists of laboratory testing, radiographic imaging, and pulmonary function testing.

18. Investigations Bacteriological and mycological examination of sputum Radiological examination Bronchiectasis, unless very gross, is not usually apparent on a chest X-ray. In advanced disease, thickened airway walls , cystic bronchiectatic spaces, and associated areas of pneumonic consolidation or collapse may be visible. CT is much more sensitive, and shows thickened dilated airways .

19. CT Findings [1] The main diagnostic features are: 1) internal diameter of a bronchus is wider than its adjacent pulmonary artery; 2) failure of the bronchi to taper; and 3) visualization of bronchi in the outer 1–2 cm of the lung fields McGuinness G, Naidich DP. CT of airways disease and bronchiectasis.Radiol Clin North Am. 2002;40:1–19.

20. Investigation: Assessment of ciliary function A screening test can be performed in patients suspected of having a ciliary dysfunction syndrome by measuring the time taken for a small pellet of saccharin placed in the anterior chamber of the nose to reach the pharynx, when the patient can taste it. This time should not exceed 20 minutes but is greatly prolonged in patients with ciliary dysfunction. Structural abnormalities of cilia can be detected by electron microscopy.

21. Lung function tests Pulmonary function testing is used for functional assessment of impairment due to bronchiectasis. Spirometry before and after the administration of a bronchodilator is satisfactory in most patients. Obstructive impairment ( ie , reduced or normal forced vital capacity [FVC], low forced expiratory volume [FEV1], and low FEV1/FVC )is the most frequent finding.

22. Management In patients with airflow obstruction, inhaled bronchodilators and corticosteroids should be used to enhance airway patency. Physiotherapy Patients should be instructed on how to perform regular daily physiotherapy to assist the drainage of excess bronchial secretions .

23. Antibiotic therapy For most patients with bronchiectasis, the appropriate antibiotics are the same as those used in COPD; however, in general, larger doses and longer courses are required , while resolution of symptoms is often incomplete. For Pseudomonas, oral ciprofloxacin (250-750 mg 12-hourly) or ceftazidime iv (1-2 g 8-hourly). Haemoptysis in bronchiectasis often responds to treating the underlying infection , although in severe cases percutaneous embolisation of the bronchial circulation may be necessary.

24. Surgical treatment Excision of bronchiectatic areas is only indicated in a small proportion of cases. These are usually young patients in whom the bronchiectasis is unilateral and confined to a single lobe or segment on CT. Unfortunately, many of the patients in whom medical treatment proves unsuccessful are also unsuitable for surgery because of either extensive bronchiectasis or coexisting chronic lung disease. In progressive forms of bronchiectasis, resection of destroyed areas of lung which are acting as a reservoir of infection should only be considered as a last resort.

25. Major indications & Goals for Surgery Removal of destroyed lung partially obstructed by a tumor or the residue of a foreign body Reduction in acute infective episodes Reduction in overwhelming purulent and viscid sputum production Elimination of bronchiectatic airways subject to uncontrolled hemorrhage Removal of an area suspected of harboring resistant organisms such as MAC or multidrug resistant tuberculosis .

26. Prevention  Less clear and not well studied is the role of so-called preemptive, suppressive, or preventive antibiotic regimens. Examples of such regimens are listed in order of increasing complexity and expense. Strategy 1 – Daily oral antibiotic Rx, such as  ciprofloxacin  ( 500-1500  mg/day in 2-3divided doses) [  1  ]. Alternatively, a similar antibiotic given for 7-14 d/ mnth . Strategy 2 – Daily or 3X wkly use of a macrolide antibiotic , a modification of Strategy 1 that is efficacious in the management of cystic fibrosis [  2  ]. The benefit of this approach was demonstrated in a double-blind trial that randomly assigned 19 patients with bronchiectasis to receive erythromycin (500 mg, twice per day) or placebo for eight weeks [  3  ]. Rayner CF, Tillotson G, Cole PJ, Wilson R. Efficacy and safety of long-term ciprofloxacin in the management of severe bronchiectasis. J Antimicrob Chemother 1994; 34:149. Saiman L, Marshall BC, Mayer- Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 2003; 290:1749. Tsang KW, Ho PI, Chan KN, et al. A pilot study of low-dose erythromycin in bronchiectasis. Eur Respir J 1999; 13:361.

27. Prognosis The disease is progressive when A/W ciliary dysfunction and cystic fibrosis, and eventually causes respiratory failure. In other patients the prognosis can be relatively good if physiotherapy is performed regularly and antibiotics are used aggressively.

28. SUMMARY AND RECOMMENDATIONS Bronchiectasis is a syndrome of chronic cough and daily viscid sputum production associated with airway dilatation and bronchial wall thickening. Exacerbations are usually caused by acute bacterial infections. For outpatients with an acute exacerbation and no history of recurrent exacerbations, we suggest initiation of a fluoroquinolone antibiotic, rather than an alternative oral antibiotic ( Grade 2B ). For hospitalized patients with an acute exacerbation, we suggest initiation of two intravenous antibiotics with efficacy for Pseudomonas ( Grade 2B ). The antibiotics should have different mechanisms of killing. For all patients (outpatients and inpatients) with an acute exacerbation and a history of recurrent exacerbations, we suggest the initial antibiotic choice be tailored to prior sputum cultures and sensitivities, rather than chosen empirically ( Grade 2C ). For patients with an acute exacerbation, we suggest at least seven to ten days of antibiotic therapy ( Grade 2C ). Source: uptodate 21.6

29. SUMMARY AND RECOMMENDATIONS For patients who have recurrent exacerbations, we suggest preventive antibiotics, rather than waiting until an exacerbation occurs to initiate antibiotic therapy ( Grade 2B ). Our threshold for the initiation of preventive antibiotics is three or more exacerbations within one year. We suggest that all patients with bronchiectasis receive chest physiotherapy ( Grade 2B ). We suggest not using inhaled glucocorticoids for patients with bronchiectasis except in the presence of distressing wheeze and cough ( Grade 2C ). Systemic glucocorticoids should be reserved for acute exacerbations and should accompany antibacterial therapy. For patients with non-cystic fibrosis-related bronchiectasis, we recommend NOT using dornase (  DNAse  ) as a mucolytic agent ( Grade 1A ). There are insufficient data to advocate routine use of bronchodilators or pulmonary rehabilitation in patients with bronchiectasis. For patients with life-threatening hemoptysis due to bronchiectasis, we suggest bronchial artery embolization rather than surgery, if an interventional radiology service is available ( Grade 2C ). Surgical therapy is appropriate if bronchial artery embolization fails or cannot be attempted in a timely fashion. Surgical extirpation and lung transplantation should be considered on a case-by-case basis.  Source: uptodate 21.6

30. Extra notes

31. Grades Recommendation grades 1. Strong recommendation : Benefits clearly outweigh the risks and burdens (or vice versa) for most, if not all, patients 2. Weak recommendation : Benefits and risks closely balanced and/or uncertain Evidence grades A. High-quality evidence : Consistent evidence from randomized trials, or overwhelming evidence of some other form B. Moderate-quality evidence : Evidence from randomized trials with important limitations, or very strong evidence of some other form C. Low-quality evidence : Evidence from observational studies, unsystematic clinical observations, or from randomized trials with serious flaws

32. Pink Puffers Vs Blue BLoaters Pic s ource : sterilegauze.tumblr.com

33. Blue bloaters Vs Pink Puffers Symptoms Signs Complications Bronchitis Blue bloaters Chronic productive cough Purulent sputum Hemoptysis Mild dyspnea initially Cyanotic (secondary to hypoxaemia and hypercapnia) Peripheral edema (from RHF: corpulmonale ) Crackles, wheezes Frequently obese Secondary polycythemia due to hypoxaemia Pul HTN due to reactive vasoconstriction due to hypoxia Cor pulmonale from chronic pul HTN Emphysema Pink Puffers Dyspnea Minimal cough Tachypnea Pink skin Purse lip breathing Accessory muscles use Cachexic due to Anorexia+ increase work of breathing Hyperinflation/barrel cheast Hyrerresonant percussion Decrease breath sounds Diaphragmatic excursions Pneumothorax due to formation of bullae Weight loss due to increased work of breathing

34. Extra notes: Causes of Chronic cough A  chronic cough  is usually defined as a  cough  that lasts for eight weeks or longer.

35. Types of Sputum Reference: Mcleods

36. Terms Dyspnea: Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity .(ref: American thoracic society) Orthopnea: Dyspnea that worsens in lying flat position and gets relieved by sitting position. Platypnea : Dyspnea that is relieved when lying down , and worsens when sitting or standing up. Trepopnia : Dyspnea while lying on one side but not on the other ( lateral recumbent position) Tachypnea: refers to abnormally fast breathing rate . Bradypnea : refers to abnormally slow breathing rate . Tachypnoea > 15/min (Source: Mcleods ) Bradypnea : <12 (source: Mosby)

37. Respiratory Disease Restrictive Parenchymal Extraparenchymal COPD Asthma Bhrinchiectasis Bronchiloitis Cystic fibrosis Neuromuscular diseases Diphragmatic palsy GB syndrome Muscular dystrophy Cervical spine injury Chest wall Obesity Kyphoscoliosis Ankylosing spondyltis Sarcoidosis Pneumoconiosis Idiopathic pul fibrosis Drugs/ radiation induced ILD Obstructive

38. Obstructive vs Restrictive diseases PFT Results Obstructive Pattern Restrictive Pattern FEV1 Decreased (<80 %) Decreased out of proportion to FVC Decreased (may be preserved) Decreased in proportion to FVC FVC Decreased (may be preserved) Decreased (<80% predicted) FEV1/FVC Decreased (<0.7) Normal or Increased TLC Elevated Decreased DLCO Normal Decrease in Emphysema Decreased in Intrinsic restrictive lung disease Normal in neuromuscular/chest wall conditions RV Increased Decreased VC Decreased Decreased

39. Severity: Obstructive Vs Restrictive

40. Extra Notes Pattern TLC RV VC FEV1/FVC Compliance Obstructive ↑ ↑ ↓ ↓(<0.7) Unchanged except Emphyesema (↑) Restrictive ↓ ↓ ↓ N/↑ ↓↓ Obstructive Restrictive COPD Asthma Bronchiectasis Cystic fibrosis Bronchiolitis Lung fibrosis Pneumoconiosis Drugs: Amaidarone , MTX ARDS TB Low compliance indicates a stiff lung (one with high elastic recoil) and can be thought of as a thick balloon -fibrosis . High compliance indicates a pliable lung (one with low elastic recoil) and can be thought of as a grocery bag - emphysema . Hallmark of OAD: Decrease in expiratory flow rate Hallmark of RLD: Decrease in TLC & VC

41. End of Extra notes

42. End of slides References: Davidsons Uptodate 21.6 Medscape Other literature references included in slides