When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

Think of invasive pulmonary aspergillosis (IPA) in your patient when she or he has a COPD exacerbation that appears refractory to broad-spectrum antibiotics and high doses of steroids. Heighten your suspicion even more in patients with severe-steroid dependent COPD, presence of a new pulmonary infiltrate or isolation of Aspergillus spp from respiratory cultures. 1

It’s worth remembering that although dyspnea and bronchospasm are found in most COPD patients with IPA, in contrast to haematological patients, fever, chest pain and hemoptysis are usually absent in this patient population.1

Diagnosis of IPA in this patient population is challenging for several reasons including: 1. A definitive or “proven” diagnosis requires histopathologic evidence of Aspergillus invasion of lung tissue which is not possible without subjecting an already fragile patient to invasive procedures (eg, lung aspiration or biopsy); 2. In contrast to IPA in highly susceptible immunocompromised patients with cancer and recipients of hematopoietic stem cell transplants, standardized definition of IPA in patients with COPD is lacking; 1,3 and 3. Frequent colonization of the respiratory tract of COPD patients with Aspergillus spp (16.3 per 1000 COPD admission in 1 study) 4,5, makes it difficult to diagnose IPA based on cultures alone.

Aside from respiratory cultures, another non-invasive test, serum galactomannan (GM, a polysaccharide antigen that exists primarily in the cell walls of Aspergillus spp and released into the blood during its growth phase 6) may have some utility in suggesting IPA in COPD patients, albeit with a mediocre sensitivity (~30-60%) but respectable specificity (>80 %). In contrast, bronchoalveolar lavage fluid GM may have better sensitivity  (~75%-90%) with similar specificity as that of serum GM in the diagnosis of IPA in these patients 7-8

Bonus pearl: Did you know that the incidence of IPA appears to be increasing in COPD patients requiring ICU admission, with reported mortality rates of 67% to 100%? 7

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References

  1. Bulpa P, Dive A, Sibille Y. Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Eur Res J 2007;30:782-800. https://www.ncbi.nlm.nih.gov/pubmed/17906086
  2. Bulpa P, Bihin B, Dimopoulos G, et al. Which algorithm diagnoses invasive pulmonary aspergillosis best in ICU patietns with COPD? Eur Resir J 2017;50:1700532 https://www.ncbi.nlm.nih.gov/pubmed/28954783
  3. Barberan J, Garcia-Perez FJ, Villena V, et al. Development of aspergillosis in a cohort of non-neutropenic, non-transplant patients colonized by Aspergillus spp. BMC Infect Dis 2017;17:34. https://link.springer.com/article/10.1186/s12879-016-2143-5
  4. Guinea J, Torres-Narbona M, Gijon P, et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin Microbiol Infect 2010; 16:870-77. https://www.sciencedirect.com/science/article/pii/S1198743X14617432
  5. Blot Stijn I, Taccone FS, Van den Abeele A-M, et al. A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients. Am J Respir Crit Care Med 202;186:56-64. https://www.atsjournals.org/doi/full/10.1164/rccm.201111-1978OC
  6. Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006;42:1417-27. https://academic.oup.com/cid/article/42/10/1417/278148
  7. He H, Ding L, Sun B, et al. Role of galactomannan determinations in bronchoalveolar lavage fluid samples from critically ill patients with chronic obstructive pulmonary disease for the diagnosis of invasive pulmonary aspergillosis: a prospective study. Critical Care 2012;16:R138. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066034/
  8. Zhou W, Li H, Zhang Y, et al. Diagnostic value of galactomannan antigen test in serum and bronchoalveolar lavage fluid samples from patients with nonneutropenic invasive pulmonary aspergillosis. J Clin Microbiol 2017;55:2153-61. https://www.ncbi.nlm.nih.gov/pubmed/28446576
When should I suspect invasive pulmonary aspergillosis in my patient with COPD exacerbation?

My patient with COPD exacerbation has an elevated venous blood PCO2. How accurate is the peripheral venous blood gas PC02 in patients with hypercarbia?

Short answer: Not as accurate as we might like! An elevated venous pC02 is a good indicator of the presence of arterial hypercarbia but beyond that if you really want to know what the arterial pC02 is in your patient with hypercarbia, you should get an arterial blood gas (ABG).

 
A meta-analysis of studies involving patients with COPD presenting to the emergency department (ED) found a good agreement for pH and bicarbonate values between arterial and venous blood gases but not for pC02 or p02 (1). More specifically, the 95% limit of agreement varied widely from -17 to +26 mmHg between venous and arterial pC02 (average difference ~6.0 mm). In the same study, a venous pC02 of ~45 mmHg or less correctly identified patients who were hypercarbic based on ABG. Similar results have been reported by other studies involving patients with COPD exacerbation (2,3).

 
Another meta-analysis involving all comers (COPD and non-COPD patients) concluded that venous pC02 should not be used as a substitute for arterial pC02 when accurate pC02 is required (4). In fact, they emphasized that venous pC02 was not always greater than arterial pC02!

 
Bonus pearl: Did you know that an unexpectedly low bicarbonate level in a patient with COPD and CO2 retention should alert us to the possibility of concurrent metabolic acidosis (eg, due to lactic acidosis, uremia)?

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References
1. Lim BL, Kelly AM. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department. Eur J Emerg Med 2010;17:246-48. https://journals.lww.com/euro-emergencymed/Abstract/2010/10000/A_meta_analysis_on_the_utility_of_peripheral.2.aspx
2. McCanny P, Bennett K, Staunton P, et a. Venous vs arterial blood gases in the assessment of patients presenting with an exacerbation of chronic obstructive pulmonary disease. Am J Emerg Med 2012;30:896-900. https://www.sciencedirect.com/science/article/abs/pii/S0735675711002865
3. McKeevere TM, Hearson G, Housely G, et al. Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study. Thorax 2016;71:210-15. https://www.researchgate.net/publication/285545995_Using_venous_blood_gas_analysis_in_the_assessment_of_COPD_exacerbations_A_prospective_cohort_study
4. Byrne AL, Bennett M, Chatterji R, et al. Peripheral venous and arterial blood gas analysis in adults:are they comparable? A systematic review and meta-analysis. Respirology 2014;19:168-75. https://onlinelibrary.wiley.com/doi/full/10.1111/resp.12225

My patient with COPD exacerbation has an elevated venous blood PCO2. How accurate is the peripheral venous blood gas PC02 in patients with hypercarbia?

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

The answer is “NO”! With an estimated 20% to 50% of acute chronic obstructive pulmonary disease (COPD) exacerbations attributed to noninfectious factors (1,2), routine inclusion of antibiotics in the treatment of this condition is not only unnecessary but potentially harmful.

 
Although the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommends the use of antibiotics in patients who have dyspnea, increased sputum volume, and increased sputum purulence—or at least 2 of these 3 criteria when sputum purulence is one of them (3)—, these recommendations are not based on robust evidence and have not been widely corroborated (2,4-6).

 
That’s why the findings of a 2019 New England Journal of Medicine study (PACE) supporting the use of serum C-reactive protein (CRP) as an adjunctive test in COPD exacerbation is particularly welcome (1). In this multicenter randomized controlled trial performed in the U.K., the following CRP guidelines (arrived from prior studies) were provided to primary care clinicians to be used as part of their decision making in determining which patients with COPD exacerbation may not need antibiotic therapy:

 
• CRP less than 20 mg/L: Antibiotics unlikely to be beneficial
• CRP 20-40 mg/L: Antibiotics may be beneficial, mainly if purulent sputum is present
• CRP greater than 40 mg/L: Antibiotics likely to be beneficial

 
Adoption of these guidelines resulted in significantlly fewer patients being placed on antibiotics without evidence of harm over a 4-week follow-up period (1).  Despite its inherent limitations (eg, single country, outpatient setting), CRP testing may be a step in the right direction in curbing unnecessary use of antibiotics in COPD exacerbation.  

 

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References

 
1. Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med 2019;381:111-20. https://www.ncbi.nlm.nih.gov/pubmed/31291514
2. Llor C, Moragas A, Hernandez S, et al. Efficacy of antibiotic therapy for acute exacerbations of mild to moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2012;186:716-23. https://www.ncbi.nlm.nih.gov/pubmed/22923662
3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. GOLD, 2019 (http://www.goldcopd.org).
4. Brett AS, Al-Hasan MN. COPD exacerbations—A target for antibiotic stewardship. N Engl J Med 2018;381:174-75. https://www.ncbi.nlm.nih.gov/pubmed/31291521
5. Miravitlles M, Moragas A, Hernandez S, et al. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest 2013;144:1571-7. https://www.ncbi.nlm.nih.gov/pubmed/23807094
6. Van Vezen P, Ter Riet G, Bresser P, et al. Doxycycline for outpatient-treated acute exacerbations of COPD: a randomized double-blind placebo-controlled trial. Lancet Respir Med 2017;5:492-9. https://www.ncbi.nlm.nih.gov/pubmed/28483402

Should I routinely treat my patients with acute COPD exacerbation with antibiotics?

Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

Although there are no consensus guidelines on when to evaluate patients with COPD for antibody deficiency, we should at least consider this possibility in patients with recurrent exacerbations despite maximal inhaled therapy (long-acting beta-2 agonist-LABA, long-acting muscarinic antagonist-LAMA and inhaled corticosteroids).1

Couple of retrospective studies of common variable immunodeficiency (CVID) in patients with COPD have reported a prevalence ranging from 2.4% to 4.5%. 1 In another study involving 42 patients thought to have had 2 or more moderate to severe COPD exacerbations per year—often despite maximal inhaled therapy— 29 were diagnosed  with antibody deficiency syndrome, including 20 with specific antibody deficiency (SAD), 8 with CVID and 1 with selective IgA deficiency.2  Although systemic corticosteroids may lower IgG and IgA levels, the majority of the patients in this study were not taking any corticosteroids at the time of their evaluation.

In another study involving patients undergoing lung transplantation, pre-transplant mild hypogammaglobulinemia was more prevalent among those with COPD (15%) compared to other lung conditions (eg, cystic fibrosis), independent of corticosteroid use.3  A favorable impact of immunoglobulin therapy or chronic suppressive antibiotics on reducing recurrent episodes of COPD exacerbation in patients with antibody deficiency has also been reported, supporting the clinical relevance of hypogammaglobulinemia in these patients. 2,4 

Remember that even normal quantitative serum immunoglobulin levels (IgG, IgA, and IgM) do not necessarily rule out antibody deficiency. Measurement of IgG subclasses, as well as more specific antibodies, such as those against pneumococcal polysaccharides may be required for further evaluation.

See a related pearl at https://pearls4peers.com/2015/07/12/my-65-year-old-patient-has-had-several-bouts-of-bacterial-pneumonia-in-the-past-2-years-her-total-serum-immunoglobulins-are-within-normal-range-could-she-still-be-immunodeficient/.

Contributed in part by Sydney Montesi, MD, Mass General Hospital, Boston, MA.

References

  1. Berger M, Geng B, Cameron DW, et al. Primary immune deficiency diseases as unrecognized causes of chronic respiratory disease. Resp Med 2017;132:181-188. https://www.sciencedirect.com/science/article/pii/S0954611117303554
  2. McCullagh BN, Comelias AP, Ballas ZK, et al. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD). PLoS ONE 2017; 12: e0172437. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0172437
  3. Yip NH, Lederer DJ, Kawut SM, et al. Immunoglobulin G levels before and after lung transplantation 2006;173:917-21.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662910/
  4. Cowan J, Gaudet L, Mulpuru S, et al. A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease. PLoS ONE 2015;10:e0142205. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142205

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Should my patient with COPD and recurrent exacerbations undergo evaluation for antibody deficiency?

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?

The most consistent risk factor for isolation of P. aeruginosa from sputum of adults with COPD is the presence of more advanced pulmonary disease (eg, FEV-1 <35%-50% of predicted value) or functional impairment (1-5).

 

Chronic corticosteroid use is also frequently cited as an important predictor of respiratory tract colonization/infection due to P. aeruginosa in patients with COPD, while the data on antibiotic use during the previous months have been conflicting (2,4). Other risk factors may include prior isolation of P. aeruginosa and hospital admission during the previous year (1).

 
A prospective study of patients hospitalized for COPD exacerbation found P. aeruginosa to be the most frequently isolated organism, growing from 26% of validated sputum samples at initial admission, followed by Streptococcus pneumoniae and Hemophilus influenzae. In the same study, bronchiectasis (present in up to 50% of patients with COPD) was not shown to be independently associated with the isolation of P. aeruginosa (1).

 
Of interest, compared to the patients without P. aeruginosa, patients hospitalized for acute exacerbation of COPD and isolation of P. aeruginosa from sputum have significantly higher mortality: 33% at 1 year, 48% at 2 years and 59% at 3 years (5).

 

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References
1. Garcia-Vidal C, Almagro P, Romani V, et al. Pseudomonas aeruginosa in patients hospitalized for COPD exacerbation: a prospective study. Eur Respir J 2009;34:1072-78. https://www.ncbi.nlm.nih.gov/pubmed/19386694
2. Murphy TF. Pseudomonas aeruginosa in adults with chronic obstructive pulmonary disease. Curr Opin Pulm Med 2009;15:138-42. https://www.ncbi.nlm.nih.gov/pubmed/19532029
3. Miravitlles M, Espinosa C, Fernandez-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999;116:40-6. https://www.ncbi.nlm.nih.gov/pubmed/10424501
4. Murphy TF, Brauer AL, Eschberger K, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:853-60. https://www.ncbi.nlm.nih.gov/pubmed/18202344
5. Almagro P, Silvado M, Garcia-Vidal C, et al. Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 2012;84:36-43. https://www.karger.com/Article/FullText/331224

 

 

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?

Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?

Patients admitted to the hospital for acute exacerbation of COPD are generally regarded as being at high risk of venous thromboembolism (VTE) (prevalence 5%-29%), possibly due to the frequent coexistence of other risk factors, such as immobility, history of smoking, and venous stasis.1 The exact mechanism(s) behind this association remains poorly understood, however.

Among patients with moderate-very severe COPD (GOLD criteria stage II-IV),  high BMI, low exercise tolerance, history of pneumothorax, congestive heart failure, and peripheral vascular disease have also been associated with VTE.1

Systemic inflammation has also been implicated in increasing the risk of VTE in patients with COPD. Although the pathophysiology of COPD is largely defined by the local inflammatory response to airway injury, evidence suggests that there is also a systemic inflammatory response in COPD.2,3 This systemic inflammation could in turn contribute to the increased risk of vascular disease, including VTE, coronary artery disease, and cerebrovascular disease.4

Bonus pearl: Did you know that VTE may be 3x more prevalent among patients with COPD exacerbation without known cause (vs those with identifiable cause) and is associated with a 1-year mortality of 61.9%! 5

References:

  1. Kim V, Goel N, Gangar J, et al. Risk factors for venous thromboembolism in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis 2014;1: 239-249. https://www.ncbi.nlm.nih.gov/pubmed/25844397
  2. Lankeit M, Held M. Incidence of venous thromboembolism in COPD: linking inflammation and thrombosis? Eur Respir J 2016;47(2):369-73. https://www.ncbi.nlm.nih.gov/pubmed/26828045
  3. Sinden NJ1, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence. Thorax 2010;65:930-6. https://www.ncbi.nlm.nih.gov/pubmed/20627907
  4. King PT. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clinical and Translational Medicine 2015;4:26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518022/
  5. Gunen H, Gulbas G, In E, et al. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;36:1243-8.  https://www.ncbi.nlm.nih.gov/pubmed/19926740 

Contributed by Camilo Campo, Medical Student, Harvard Medical School, Boston, MA.

Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

The mechanism behind digital clubbing has yet to be fully elucidated, with hypotheses ranging from a circulating vasodilator, tissue hypoxia, a neurocirculatory reflex, and genetic factors. 1 Although hypoxemia is often cited as a cause of clubbing, it is often absent in the presence of clubbing and many patients with hypoxemia do not have clubbing.

A potentially unifying pathophysiologic mechanism of clubbing revolves around platelet clustering and associated growth factor release. 2.3 Platelet clumps/megakaryocytes—either because of circumvention of the lung capillary network (eg, in intracardiac shunts or lung cancer) or increased production (eg, in left-sided endocarditis or chronic inflammatory conditions)—may wedge in the fine vasculature of distal fingertips or toes and cause release of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).

Together, PDGF and VEGF promote neovascularization, increase vessel dilation and permeability, and modify connective tissue to create the distinct club-like appearance. Local hypoxic condition from reduced capillary perfusion is thought to further stimulate the release of these growth factors.

Potential causes of clubbing in our patient include lung cancer, interstitial lung disease, bronchiectasis, core pulmonale and secondary polycythemia, among many others. 1

Fun Fact: Did you know that clubbing, also known as “Hippocratic finger”, was first described by Hippocrates in a patient with chronic empyema (don’t ask how chronic empyema was diagnosed in 400 BC!)?1

 

References

  1. McPhee SJ. Clubbing. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths;1990. Chapter 44. Available from https://www.ncbi.nlm.nih.gov/books/NBK366/
  2. Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger clubbing. Lancet 1987;2:1434-4. https://www.ncbi.nlm.nih.gov/pubmed/2891996/ 
  3. Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing. J Pathol 2004;203:721-8. https://www.ncbi.nlm.nih.gov/pubmed/15141388

 

Contributed by George Bugarinovic, Medical Student, Harvard Medical School

My patient with COPD has new clubbing of his finger tips. What is the mechanism of clubbing?

How does azithromycin (AZ) benefit patients with severe COPD or cystic fibrosis (CF)?

AZ is a macrolide antibiotic which interferes with bacterial protein synthesis by binding to the 50S ribosomal subunit. It is often used to treat acute respiratory tract infections due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, as well as Mycoplasma, Chlamydia, and Legionella sp1. Although it has no in vitro activity against many aerobic gram-negative bacilli such as Pseudomonas aeruginosa, its chronic use has often been associated with a significant reduction in the frequency of disease exacerbations in patients with chronic bronchiectasis and colonization due to this organism, including patients with COPD or CF1-3.

Because P. aeruginosa is invariably macrolide-resistant, the beneficial effect of AZ in chronically infected or colonized patients must be due to factors other than its direct effect on bacterial replication.  Several mechanisms have been invoked including: 1. Inhibition of quorum-sensing dependent virulence factor and biofilm production 2.Blunting of host inflammatory response (eg, ↑IL-10, and ↓ IL-1ß, IL-6, IL-8, TNF-α, and ↓ chemotaxis); and 3. Enhanced antiviral response1.

The latter finding is quite unexpected but AZ appears to augment interferon response to rhinovirus in bronchial cells of COPD patients3.  With respiratory viruses (including rhinoviruses) causing 20-55% of all COPD exacerbations, perhaps this is another way AZ may help the host! Who would have thought!!

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References

  1. Vos R, Vanaudenaerde BM, Verleden SE, et al. Anti-inflammatory and immunomodulatory properties of azithromycin involved in treatment and prevention of chronic lung allograft rejection. Transplantation 2012;94:101-109.
  2. Cochrane review. Treatment with macrolide antibiotics for people with cystic fibrosis and chronic chest infection. Nov 14, 2012. http://www.cochrane.org/CD002203/CF_treatment-with-macrolide-antibiotics-for-people-with-cystic-fibrosis-and-chronic-chest-infection
  3. Menzel M, Akbarshahi H, Bjermer L, et al. Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD. Scientific Reports 2016; 6:28698. DOI:10.1038/srep 28698.

 

 

How does azithromycin (AZ) benefit patients with severe COPD or cystic fibrosis (CF)?

What are the benefits and risks of inhaled dual anticholinergic therapy (IDAT) in patients admitted to the hospital with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?

Patients admitted with AECOPD are commonly on maintenance tiotropium and are frequently treated with additional inhaled anticholinergic agents (eg, ipratropium) during hospitalization. However, the scientific evidence justifying IDAT in patients with AECOPD is lacking, and is quite limited even in patients with stable COPD1-3.   Two small, randomized double-blind studies compared the impact of tiotropium combined with either ipratropium or placebo in outpatients with stable COPD.  Both studies selected FEV1 alone as their primary end-point and found only a marginal benefit with IDAT2,3

A population-based study of acute urinary retention in persons with COPD aged ≥66 years found a significantly higher odds of acute urinary retention among those on IDAT vs monotherapy or no anticholinergics (odds ratios 1.4 and 2.7, respectively)4.

In short, routine use of IDAT in patients with AECOPD lacks firm evidence in its clinical efficacy and may be associated with acute urinary retention.

 

References                                                                                                                                                               

 

  1. Cole JM, Sheehan AH, Jordan JK. Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease. Ann Pharmacother 2012;46:1717-21.
  2. Kerstjens HA, Bantje TA, Luursema PB, Sinninghe Damste HE, de Jong JW. Effects of short-acting bronchodilators added to maintenance tiotropium therapy. Chest 2007;132:1493-9.
  3. Cazzola M, Santus P, D’Adda A, et al. Acute effects of higher than standard doses of salbutamol and ipratropium on tiotropium-induced bronchodilation in patients with stable COPD. Pulm Pharmacol Ther 2009; 22:177-82.
  4. Singh S, Furbergt CD. Inhaled anticholinergic drug therapy and the risk of acute urinary retention in chronic obstructive pulmonary disease. Arch Intern Med 2011;171:920-2.

 

Contributed by Josh Ziperstein, MD, Massachusetts General Hospital, Boston.

What are the benefits and risks of inhaled dual anticholinergic therapy (IDAT) in patients admitted to the hospital with a diagnosis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD)?

Should my patient with chronic obstructive pulmonary disease (COPD) who emigrated from Latin America over 20 years ago undergo testing for Strongyloides infection (SI)?

Worldwide prevalence of SI may be as high as 100 million people, with an increasing number seen in developed countries among immigrants (including those from Latin America), refugees, and travelers. “Autoinfection” by Strongyloides allows it to complete its life cycle between the GI tract and the lung without leaving the host, and is often associated with chronic asymptomatic infection in the immunocompetent persons1.

Immunocompromised patients, however, particularly those treated with corticosteroids (including systemic courses as short as 6 days, or local injection)  are at increased risk of developing an accelerated form of autoinfection due to SI, also known as  hyperinfection syndrome (HIS)1,2.  HIS has been reported as late as 64 years after leaving an endemic  area!1.   When Strongyloides larvae disseminate away from the lung or GI tract into other organs (e.g. brain) the mortality rate may approach 100%, if untreated.

Due to the potential complications associated with untreated SI, particularly in the immunocompromised , routine screening of anyone with a potential Strongyloides-exposure history (irrespective of symptoms or years since exposure) has been advocated1,3.  In our patient with COPD, screening for asymptomatic SI by a highly sensitive test (eg serology) should be considered (as early as possible if corticosteroids are being considered for treatment of his COPD).  Some have also advocated empiric treatment with ivermectin in “at risk patients” in whom testing is not feasible or practical1,4.

 

References

  1. Mejia R, Nutman TB. Screening, prevention, and treatment for hyperinfection syndrome and disseminated infections caused by Strongyloides stercoralis. Curr Opin Infect Dis 2012;25:458-463.
  2. Keiser PB, Nutman TB. Strongyloides stercoralis in the immunocompromised population. Clin Microbiol Rev 2004;17:208-217.
  3. CDC. Strongyloides. http://www.cdc.gov/parsites/strongyloides/helath_professionals/ , accessed September 20, 2016.
  4. Santiago M, Leitão B. Prevention of strongyloides hyperinfection syndrome: a rheumatologic point of view. Eur J Intern Med 2009;20:744-748.
Should my patient with chronic obstructive pulmonary disease (COPD) who emigrated from Latin America over 20 years ago undergo testing for Strongyloides infection (SI)?