Bronchiectasis medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Bronchiectasis}} | {{Bronchiectasis}} | ||
{{CMG}} | {{CMG}}; {{AE}} {{HQ}}, Saarah T. Alkhairy, M.D. | ||
==Overview== | ==Overview== | ||
The management of bronchiectasis includes [[Medicine|medical]] therapy and [[Physical therapy|physiotherapy]] strategies. The medical treatment consists of patient [[education]], treatment of the acute exacerbations, prophylactic treatment, [[vaccination]], and other therapies. Antimicrobial therapy is indicated for acute exacerbations of bronchiectasis. The [[Physical therapy|physiotherapy]] strategies focus on airway clearance and [[Lung|pulmonary]] rehabilitation. Supportive therapies include inhaled [[mannitol]], nebulized hypertonic 7% saline, inhaled [[corticosteroids]], and [[oxygen]] therapy. Along with treatment of bronchiectasis, it is important to treat any underlying conditions. | |||
==Medical Therapy== | ==Bronchiectasis Medical Therapy== | ||
===Medical Treatment=== | |||
====Patient Education ==== | |||
*The patients should understand their [[diagnosis]] clearly. | |||
* [[Smoking]] cessation, regular [[physical exercise|exercise]], and proper [[nutrition]] should be advised. | |||
*The patient should know how to self-manage acute exacerbations with a home supply of [[antibiotic|antibiotics]]. | |||
====Treatment of Acute Exacerbations==== | |||
*The mainstay of treatment is [[antibiotic]] therapy. | |||
*Once the [[sputum]] specimen is collected and sent for culture, a targeted [[antibiotic]] therapy is recommended. | |||
*It is considered chronic if the same [[microorganism]] is detected in three or more consecutive cultures separated by at least 1 month over a period of 6 months.<ref name="pmid23728208">{{cite journal| author=McDonnell MJ, Ward C, Lordan JL, Rutherford RM| title=Non-cystic fibrosis bronchiectasis. | journal=QJM | year= 2013 | volume= 106 | issue= 8 | pages= 709-15 | pmid=23728208 | doi=10.1093/qjmed/hct109 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23728208 }} </ref> | |||
*[[Intravenous]] (IV) antibiotics may be needed if there has been: no response to oral antibiotics, systemic deterioration, or if the organism is sensitive only to IV agents.<ref name="pmid23728208">{{cite journal| author=McDonnell MJ, Ward C, Lordan JL, Rutherford RM| title=Non-cystic fibrosis bronchiectasis. | journal=QJM | year= 2013 | volume= 106 | issue= 8 | pages= 709-15 | pmid=23728208 | doi=10.1093/qjmed/hct109 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23728208 }} </ref> | |||
*[[Allergic bronchopulmonary aspergillosis]] (ABPA) | |||
**Oral [[prednisone]] 0.5 to 1 mg/kg per day for two weeks followed by alternate day therapy tapered over three to six months. | |||
**A 16 week course of an [[Antifungal drug|antifungal]] agent, such as [[itraconazole]] or [[voriconazole]], may be added in patients who require large doses of [[glucocorticoids]]. | |||
===Antibiotic Regimen=== | |||
*'''Bronchiectasis'''<ref name="pmid20627931">{{cite journal| author=Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non-CF Guideline Group| title=British Thoracic Society guideline for non-CF bronchiectasis. | journal=Thorax | year= 2010 | volume= 65 Suppl 1 | issue= | pages= i1-58 | pmid=20627931 | doi=10.1136/thx.2010.136119 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20627931 }} </ref> | |||
:* 1.'''Acute exacerbations of bronchiectasis''' | |||
::* 1.1 '''Empiric antimicrobial therapy''' | |||
:::* Preferred regimen: [[Amoxicillin]] 0.5-1 g PO/IV q8h for 14 days | |||
:::* Alternative regimen (1): [[Ciprofloxacin]] 500-750 mg PO bid for 14 days | |||
:::* Alternative regimen (2): [[Clarithromycin]] 500 mg PO bid for 14 days | |||
::* 1.2 '''Pathogen-directed antimicrobial therapy''' | |||
:::* 1.2.1 '''Streptococcus pneumoniae''' | |||
::::* Preferred regimen: [[Amoxicillin]] 500 mg PO tid for 14 days | |||
::::* Alternative regimen: [[Clarithromycin]] 500 mg PO bid for 14 days | |||
:::* 1.2.2 '''Haemophilus influenzae (b-lactamase negative)''' | |||
::::* Preferred regimen (1): [[Amoxicillin]] 0.5-1 g PO tid for 14 days | |||
::::* Preferred regimen (2): [[Amoxicillin]] 3 g PO bid for 14 days | |||
::::* Alternative regimen (1): [[Clarithromycin]] 500 mg PO bid for 14 days | |||
::::* Alternative regimen (2): [[Ciprofloxacin]] 500 mg PO bid for 14 days | |||
::::* Alternative regimen (3): [[Ceftriaxone]] 2 g IV q24h for 14 days | |||
:::* 1.2.3 '''Haemophilus influenzae (b-lactamase positive)''' | |||
::::* Preferred regimen: [[Amoxicillin-Clavulanate]] 625 mg PO tid for 14 days | |||
::::* Alternative regimen (1): [[Clarithromycin]] 500 mg PO bid for 14 days | |||
::::* Alternative regimen (2): [[Ciprofloxacin]] 500 mg PO bid for 14 days | |||
::::* Alternative regimen (3): [[Ceftriaxone]] 2 g IV q24h for 14 days | |||
:::* 1.2.4 '''Moraxella catarrhalis''' | |||
::::* Preferred regimen: [[Amoxicillin-Clavulanate]] 625 mg PO tid for 14 days | |||
::::* Alternative regimen: [[Ciprofloxacin]] 500 mg PO bid for 14 days | |||
:::* 1.2.5 '''Staphylococcus aureus (MSSA)''' | |||
::::* Preferred regimen: [[Flucloxacillin]] 500 mg PO qid for 14 days | |||
::::* Alternative regimen: [[Clarithromycin]] 500 mg PO bid 14 days | |||
:::* 1.2.6 '''Staphylococcus aureus (MRSA) (mild-to-moderate)''' | |||
::::* Preferred regimen (weight < 50 kg): [[Rifampicin]] 450 mg PO qd {{and}} [[Trimethoprim]] 200 mg PO bid for 14 days | |||
::::* Preferred regimen (weight > 50 kg): [[Rifampicin]] 600 mg PO qd {{and}} [[Trimethoprim]] 200 mg PO bid for 14 days | |||
::::* Alternative regimen (weight < 50 kg): [[Rifampicin]] 450 mg PO qd {{and}} [[Doxycycline]] 200 mg PO qd for 14 days | |||
::::* Alternative regimen (weight > 50 kg): [[Rifampicin]] 600 mg PO qd {{and}} [[Doxycycline]] 200 mg PO qd for 14 days | |||
::::* Alternative regimen: [[Linezolid]] 600 mg PO bid for 14 days (third-line therapy) | |||
:::* 1.2.7 '''Staphylococcus aureus (MRSA) (severe)''' | |||
::::* Preferred regimen (1): [[Vancomycin]] 1 g IV q12h (trough levels of 10-20 ng/mL) | |||
::::* Preferred regimen (2): [[Teicoplanin]] 400 mg IV q24h for 14 days | |||
::::* Alternative regimen: [[Linezolid]] 600 mg IV q12h for 14 days | |||
:::* 1.2.8 '''Coliforms (eg, Klebsiella, enterobacter)''' | |||
::::* Preferred regimen: [[Ciprofloxacin]] 500 mg PO bid for 14 days | |||
::::* Alternative regimen: [[Ceftriaxone]] 2 g IV od 14 days | |||
:::* 1.2.9 '''Pseudomonas aeruginosa''' | |||
::::* Preferred regimen: [[Ciprofloxacin]] 500-750 mg PO bid for 14 days | |||
::::* Alternative regimen (1): [[Ceftazidime]] 2 g PO tid for 14 days | |||
::::* Alternative regimen (2): [[Piperacillin-Tazobactam]] 4.5 g PO tid for 14 days | |||
::::* Alternative regimen (3): [[Aztreonam]] 2 g PO tid for 14 days | |||
::::* Alternative regimen (4): [[Meropenem]] 2 g PO tid for 14 days | |||
:::* 1.2.10 '''Pediatric Dosing''' | |||
::::* [[Amoxicillin]] 20-50 mg/kg/day PO bid or tid | |||
::::* [[Co-amoxiclav]] 20-45 mg/kg/day PO bid or tid | |||
::::* [[Trimethoprim]] 4-6 mg/kg/day PO bid (Children < 12 yr) | |||
::::* [[Trimethoprim]] 100-200 mg PO bid (Children > 12 yr) | |||
::::* [[Rifampicin]] 450 mg PO qd (weight < 50 kg) | |||
::::* [[Rifampicin]] 600 mg PO qd (weight > 50 kg) | |||
::::* [[Vancomycin]] 45-60 mg/kg/day IV q8-12h | |||
::::* [[Ciprofloxacin]] 15-30 mg/kg/day PO/IV q12h | |||
::::* [[Doxycycline]] 2-5 mg/kg/day PO/IV q12-24h (maximum daily dose: 200 mg) | |||
::::* [[Linezolid]] 10 mg/kg IV/PO q12h | |||
::::* [[Ceftriaxone]] 50-75 mg/kg IV/IM q24h | |||
::::* [[Ceftazidime]] 150 mg/kg/day IV/IM q8h | |||
:* 2. '''Long-term antibiotic prophylaxis''' | |||
:* Patients with ≥3 exacerbations/year requiring [[antibiotic]] therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long-term [[antibiotic]] prophylaxis | |||
::* 2.1 '''Pathogen-directed antimicrobial therapy''' | |||
:::* 2.1.1 '''Streptococcus pneumoniae''' | |||
::::* Preferred regimen: [[Amoxicillin]] 500 mg PO bid | |||
::::* Alternative regimen: [[Clarithromycin]] 250 mg PO bid | |||
:::* 2.1.2 '''Haemophilus influenzae (b-lactamase negative)''' | |||
::::* Preferred regimen: [[Amoxicillin]] 500 mg PO bid | |||
::::* Alternative regimen: [[Clarithromycin]] 250 mg PO bid | |||
:::* 2.1.3 '''Haemophilus influenzae (b-lactamase positive)''' | |||
::::* Preferred regimen: [[Amoxicillin-Clavulanate]] 375 mg PO tid | |||
::::* Alternative regimen: [[Clarithromycin]] 250 mg PO bid | |||
:::* 2.1.4 '''Moraxella catarrhalis''' | |||
::::* Preferred regimen: [[Amoxicillin-Clavulanate]] 375 mg PO tid | |||
::::* Alternative regimen: [[Clarithromycin]] 250 mg PO bid | |||
:::* 2.1.5 '''Staphylococcus aureus (MSSA)''' | |||
::::* Preferred regimen: [[Flucloxacillin]] 500 mg PO bid | |||
::::* Alternative regimen: [[Clarithromycin]] 250 mg PO bid | |||
:* 3. '''Pseudomonas eradication (colonization)''' | |||
::* 3.1 '''Initial therapy''' | |||
:::* Preferred regimen: [[Ciprofloxacin]] 750 mg PO bid for 14 days | |||
::* 3.2 '''Secondary therapy in case of treatment failure''' | |||
:::* Preferred regimen (1): [[Piperacillin-tazobactam]] 4.5 g PO tid for 14 days | |||
:::* Preferred regimen (2): [[Cefepime]] 1-2 g IV q8-12h | |||
:::* Preferred regimen (3): [[Ciprofloxacin]] 750 mg PO bid for 4 weeks {{and}} [[Colistin]] (Nebulized) 2 MU NEB bid for 3 months | |||
:::* Preferred regimen (3): [[Colistin]] (Nebulized) 2 MU NEB bid for 3 months | |||
[[ | ====Other Therapies==== | ||
*Inhaled [[mannitol]] and nebulized [[hypertonic]] 7% saline for increased airways clearance and [[sputum]] yield<ref name="pmid23728208">{{cite journal| author=McDonnell MJ, Ward C, Lordan JL, Rutherford RM| title=Non-cystic fibrosis bronchiectasis. | journal=QJM | year= 2013 | volume= 106 | issue= 8 | pages= 709-15 | pmid=23728208 | doi=10.1093/qjmed/hct109 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23728208 }} </ref> | |||
*Inhaled [[corticosteroids]] show a significant decrease in [[sputum]] production and [[cough]]<ref name="pmid23728208">{{cite journal| author=McDonnell MJ, Ward C, Lordan JL, Rutherford RM| title=Non-cystic fibrosis bronchiectasis. | journal=QJM | year= 2013 | volume= 106 | issue= 8 | pages= 709-15 | pmid=23728208 | doi=10.1093/qjmed/hct109 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23728208 }} </ref> | |||
*The combination of a long-acting [[Beta2-adrenergic receptor agonist|beta2-agonists]] ([[LABA]]) with a conventional inhaled [[corticosteroids]] can improve the quality of life | |||
*Oxygen therapy | |||
== Physiotherapy Strategies== | |||
====Airway Clearance==== | |||
*Postural drainage | |||
*Autogenic drainage | |||
* ActiveCycle of [[breathing]] techniques | |||
*Positive expiratory pressure (PEP) | |||
*Oscillatory PEP devices | |||
*High-frequency chest wall [[percussion]] | |||
====Pulmonary Rehabilitation==== | |||
*[[Physical exercise|Exercise]] training | |||
*[[Nutrition|Nutritional]] counseling | |||
*Education of the patient's disease and how to manage it | |||
*Techniques on how to conserve energy | |||
*Strategies on breathing | |||
*[[Psychology|Psychological]] counseling | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
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{{WH}} | |||
{{WS}} | |||
[[Category:Pulmonology]] | [[Category:Pulmonology]] | ||
[[Category: | [[Category:Medicine]] | ||
[[Category: | [[Category:Up-To-Date]] | ||
Latest revision as of 20:43, 29 July 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hamid Qazi, MD, BSc [2], Saarah T. Alkhairy, M.D.
Overview
The management of bronchiectasis includes medical therapy and physiotherapy strategies. The medical treatment consists of patient education, treatment of the acute exacerbations, prophylactic treatment, vaccination, and other therapies. Antimicrobial therapy is indicated for acute exacerbations of bronchiectasis. The physiotherapy strategies focus on airway clearance and pulmonary rehabilitation. Supportive therapies include inhaled mannitol, nebulized hypertonic 7% saline, inhaled corticosteroids, and oxygen therapy. Along with treatment of bronchiectasis, it is important to treat any underlying conditions.
Bronchiectasis Medical Therapy
Medical Treatment
Patient Education
- The patients should understand their diagnosis clearly.
- Smoking cessation, regular exercise, and proper nutrition should be advised.
- The patient should know how to self-manage acute exacerbations with a home supply of antibiotics.
Treatment of Acute Exacerbations
- The mainstay of treatment is antibiotic therapy.
- Once the sputum specimen is collected and sent for culture, a targeted antibiotic therapy is recommended.
- It is considered chronic if the same microorganism is detected in three or more consecutive cultures separated by at least 1 month over a period of 6 months.[1]
- Intravenous (IV) antibiotics may be needed if there has been: no response to oral antibiotics, systemic deterioration, or if the organism is sensitive only to IV agents.[1]
- Allergic bronchopulmonary aspergillosis (ABPA)
- Oral prednisone 0.5 to 1 mg/kg per day for two weeks followed by alternate day therapy tapered over three to six months.
- A 16 week course of an antifungal agent, such as itraconazole or voriconazole, may be added in patients who require large doses of glucocorticoids.
Antibiotic Regimen
- Bronchiectasis[2]
- 1.Acute exacerbations of bronchiectasis
- 1.1 Empiric antimicrobial therapy
- Preferred regimen: Amoxicillin 0.5-1 g PO/IV q8h for 14 days
- Alternative regimen (1): Ciprofloxacin 500-750 mg PO bid for 14 days
- Alternative regimen (2): Clarithromycin 500 mg PO bid for 14 days
- 1.2 Pathogen-directed antimicrobial therapy
- 1.2.1 Streptococcus pneumoniae
- Preferred regimen: Amoxicillin 500 mg PO tid for 14 days
- Alternative regimen: Clarithromycin 500 mg PO bid for 14 days
- 1.2.2 Haemophilus influenzae (b-lactamase negative)
- Preferred regimen (1): Amoxicillin 0.5-1 g PO tid for 14 days
- Preferred regimen (2): Amoxicillin 3 g PO bid for 14 days
- Alternative regimen (1): Clarithromycin 500 mg PO bid for 14 days
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 14 days
- Alternative regimen (3): Ceftriaxone 2 g IV q24h for 14 days
- 1.2.3 Haemophilus influenzae (b-lactamase positive)
- Preferred regimen: Amoxicillin-Clavulanate 625 mg PO tid for 14 days
- Alternative regimen (1): Clarithromycin 500 mg PO bid for 14 days
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 14 days
- Alternative regimen (3): Ceftriaxone 2 g IV q24h for 14 days
- 1.2.4 Moraxella catarrhalis
- Preferred regimen: Amoxicillin-Clavulanate 625 mg PO tid for 14 days
- Alternative regimen: Ciprofloxacin 500 mg PO bid for 14 days
- 1.2.5 Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO qid for 14 days
- Alternative regimen: Clarithromycin 500 mg PO bid 14 days
- 1.2.6 Staphylococcus aureus (MRSA) (mild-to-moderate)
- Preferred regimen (weight < 50 kg): Rifampicin 450 mg PO qd AND Trimethoprim 200 mg PO bid for 14 days
- Preferred regimen (weight > 50 kg): Rifampicin 600 mg PO qd AND Trimethoprim 200 mg PO bid for 14 days
- Alternative regimen (weight < 50 kg): Rifampicin 450 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Alternative regimen (weight > 50 kg): Rifampicin 600 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Alternative regimen: Linezolid 600 mg PO bid for 14 days (third-line therapy)
- 1.2.7 Staphylococcus aureus (MRSA) (severe)
- Preferred regimen (1): Vancomycin 1 g IV q12h (trough levels of 10-20 ng/mL)
- Preferred regimen (2): Teicoplanin 400 mg IV q24h for 14 days
- Alternative regimen: Linezolid 600 mg IV q12h for 14 days
- 1.2.8 Coliforms (eg, Klebsiella, enterobacter)
- Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
- Alternative regimen: Ceftriaxone 2 g IV od 14 days
- 1.2.9 Pseudomonas aeruginosa
- Preferred regimen: Ciprofloxacin 500-750 mg PO bid for 14 days
- Alternative regimen (1): Ceftazidime 2 g PO tid for 14 days
- Alternative regimen (2): Piperacillin-Tazobactam 4.5 g PO tid for 14 days
- Alternative regimen (3): Aztreonam 2 g PO tid for 14 days
- Alternative regimen (4): Meropenem 2 g PO tid for 14 days
- 1.2.10 Pediatric Dosing
- Amoxicillin 20-50 mg/kg/day PO bid or tid
- Co-amoxiclav 20-45 mg/kg/day PO bid or tid
- Trimethoprim 4-6 mg/kg/day PO bid (Children < 12 yr)
- Trimethoprim 100-200 mg PO bid (Children > 12 yr)
- Rifampicin 450 mg PO qd (weight < 50 kg)
- Rifampicin 600 mg PO qd (weight > 50 kg)
- Vancomycin 45-60 mg/kg/day IV q8-12h
- Ciprofloxacin 15-30 mg/kg/day PO/IV q12h
- Doxycycline 2-5 mg/kg/day PO/IV q12-24h (maximum daily dose: 200 mg)
- Linezolid 10 mg/kg IV/PO q12h
- Ceftriaxone 50-75 mg/kg IV/IM q24h
- Ceftazidime 150 mg/kg/day IV/IM q8h
- 2. Long-term antibiotic prophylaxis
- Patients with ≥3 exacerbations/year requiring antibiotic therapy or patients with fewer exacerbations that are causing significant morbidity should be considered for long-term antibiotic prophylaxis
- 2.1 Pathogen-directed antimicrobial therapy
- 2.1.1 Streptococcus pneumoniae
- Preferred regimen: Amoxicillin 500 mg PO bid
- Alternative regimen: Clarithromycin 250 mg PO bid
- 2.1.2 Haemophilus influenzae (b-lactamase negative)
- Preferred regimen: Amoxicillin 500 mg PO bid
- Alternative regimen: Clarithromycin 250 mg PO bid
- 2.1.3 Haemophilus influenzae (b-lactamase positive)
- Preferred regimen: Amoxicillin-Clavulanate 375 mg PO tid
- Alternative regimen: Clarithromycin 250 mg PO bid
- 2.1.4 Moraxella catarrhalis
- Preferred regimen: Amoxicillin-Clavulanate 375 mg PO tid
- Alternative regimen: Clarithromycin 250 mg PO bid
- 2.1.5 Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO bid
- Alternative regimen: Clarithromycin 250 mg PO bid
- 3. Pseudomonas eradication (colonization)
- 3.1 Initial therapy
- Preferred regimen: Ciprofloxacin 750 mg PO bid for 14 days
- 3.2 Secondary therapy in case of treatment failure
- Preferred regimen (1): Piperacillin-tazobactam 4.5 g PO tid for 14 days
- Preferred regimen (2): Cefepime 1-2 g IV q8-12h
- Preferred regimen (3): Ciprofloxacin 750 mg PO bid for 4 weeks AND Colistin (Nebulized) 2 MU NEB bid for 3 months
- Preferred regimen (3): Colistin (Nebulized) 2 MU NEB bid for 3 months
Other Therapies
- Inhaled mannitol and nebulized hypertonic 7% saline for increased airways clearance and sputum yield[1]
- Inhaled corticosteroids show a significant decrease in sputum production and cough[1]
- The combination of a long-acting beta2-agonists (LABA) with a conventional inhaled corticosteroids can improve the quality of life
- Oxygen therapy
Physiotherapy Strategies
Airway Clearance
- Postural drainage
- Autogenic drainage
- ActiveCycle of breathing techniques
- Positive expiratory pressure (PEP)
- Oscillatory PEP devices
- High-frequency chest wall percussion
Pulmonary Rehabilitation
- Exercise training
- Nutritional counseling
- Education of the patient's disease and how to manage it
- Techniques on how to conserve energy
- Strategies on breathing
- Psychological counseling
References
- ↑ 1.0 1.1 1.2 1.3 McDonnell MJ, Ward C, Lordan JL, Rutherford RM (2013). "Non-cystic fibrosis bronchiectasis". QJM. 106 (8): 709–15. doi:10.1093/qjmed/hct109. PMID 23728208.
- ↑ Pasteur MC, Bilton D, Hill AT, British Thoracic Society Bronchiectasis non-CF Guideline Group (2010). "British Thoracic Society guideline for non-CF bronchiectasis". Thorax. 65 Suppl 1: i1–58. doi:10.1136/thx.2010.136119. PMID 20627931.
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