Pulmonary diseases

My patient on methadone complains of lower extremity edema. Could they be related?

FA Manian MD, MPH, , , , , Leave a comment

Yes! As early as 1979, case series of patients on methadone developing peripheral edema within 3-6 months of therapy appeared in the literature1.  

Subsequent studies revealed that edema may develop from 1 week  to 6 months or longer following initiation of methadone, its severity is dose-dependent, and that it improves with reduction of methadone dose or discontinuation of therapy.  Distal extremities or the face are often involved and pulmonary edema may also occur1-3.  It is often resistant to diuretics.

The mechanism by which methadone causes peripheral edema is unclear but several hypotheses have been forwarded. The high volume of distribution and accumulation of methadone in tissues results in higher oncotic pressures in the extravascular space which in combination with reduced oncotic pressures in blood vessels due to venodilatation may lead to edema.  Other potential mechanisms include opioid-induced histamine release directly from mast cells causing venous permeability, and opioid-induced secretion of antidiuretic hormone 1-3.  

 

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References

  1. Dawson C, Paterson F, McFatter F, Buchanan D. Methadone and oedema in the palliative care setting: a case report and review of the literature. Scottish Med J 2014;59: e-11-e14. https://www.ncbi.nlm.nih.gov/pubmed/24676025.  
  2. Mahè I, Chassany O, Grenard A-S, Caulin C, Bergmann J-F. Methadone and edema: a case-report and literature review. Eur J Clin Pharmacol 2004;59:923-924. \https://www.deepdyve.com/lp/springer-journals/methadone-and-edema-a-case-report-and-literature-review-PfvnmhB1ia
  3. Kharlamb V, Kourlas H. Edema in a patient receiving methadone for chronic low back pain. Am J Health-Syst Pharm 2007;64:2557-60.https://www.ncbi.nlm.nih.gov/pubmed/18056943

 

My patient on methadone complains of lower extremity edema. Could they be related?

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

FA Manian MD, MPH, , , , , Leave a comment

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.

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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.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

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

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Simultaneous presence of PE in patients with AE-COPD is not rare, particularly in those with unexplained AE-COPD.

A recent systematic review and meta-analysis reported a pooled PE prevalence of 16.1% (95% C.I. 8.3%-25.8%) in unexplained AE-COPD, with 68% of emboli found in the main pulmonary arteries, lobar arteries or inter-lobar arteries (i.e. not subsegmental); the pooled prevalence of deep venous thrombosis (DVT) was 10.5% (95% C.I. 4.3%-19.0%) 1. Pleuritic chest pain and signs of cardiac failure were associated with AE-COPD, while symptoms suggestive of a respiratory tract infection argued against PE.

It remains unclear, however, if the threshold for evaluation of venous thromboembolism (VTE) should necessarily differ between patients with explained vs unexplained AE-COPD.

In one small study, the prevalence of VTE in “unexplained” AE-COPD was significantly higher (25%) than “explained” AE-COPD (including cases with  tracheobronchitis, pneumonia, cardiac disorders, exposure to irritant inhalants, and lack of compliance with treatment), but the VTE prevalence for the latter group was still 8.4%2.  Serum D-dimer level and Wells criteria may help exclude VTE in this patient population.

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References

  1. Aleva FE, Voets LWLM, Simons SO, et al. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. CHEST (2016), doi: 10.1016/j.chest.2016.07.034.
  2. Gunen H, Gulbas G, In E, Yetkin O, Hacievliyagil SS. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;35:1243-1248.

 

Contributed by Jeff Greenwald, MD, Core Educator Faculty, Department of Medicine, Massachusetts General Hospital

My patient with significant dyspnea appears to have an acute exacerbation of his chronic obstructive pulmonary disease (AE-COPD). How often do AE-COPD and pulmonary embolism (PE) coexist?

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?

FA Manian MD, MPH, , , , , , , Leave a comment

Active TB should be suspected based on a combination of epidemiological (eg, exposure, travel to, or residence in a high prevalence area, history of prior TB), clinical (eg, cough lasting 2-3 weeks or longer, fever, night sweats, weight loss, fatigue, less commonly, chest pain, dyspnea, and hemoptysis), chest radiograph abnormalities (eg, infiltrates, fibrosis, cavitation), and histopathologic (eg, caseating granuloma)1.

Among HIV-negative patients, the highest prevalence of TB is found those who have been incarcerated, use intravenous drugs, have alcohol use disorder, or are immunocompromised (including diabetes mellitus)2,3. 

Patients suspected of TB based on clinical criteria should undergo chest radiography.  Reactivation pulmonary TB (~90% of TB in adults) classically presents with upper lobe and/or the superior segment of the lower lobe disease.  Remember that up to 5% of patients with active pulmonary TB have normal chest radiograph, however4.  

All hospitalized patients suspected of having active TB should be placed on appropriate isolation precautions until TB is excluded.

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References

  1. Sia IG, Wieland ML. Current concepts in the management of tuberculosis. Mayo Clin Proc. 2011;86:348-361. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068897/
  2. Center for Disease Control. Tuberculosis: Data and Statistics. https://www.cdc.gov/tb/statistics/default.htm. Accessed October 3, 2016.
  3. World Health Organization. Tuberculosis. http://www.who.int/mediacentre/ factsheets/fs104/en/. Accessed October 3, 2016.
  4. Marciniuk, D, McNab, BD, Martin WT, Hoeppner, VH. Detection of pulmonary tuberculosis in patients with a normal chest radiograph. Chest 1999;115:445-452. https://journal.chestnet.org/article/S0012-3692(15)50590-4/abstract

 

 

Contributed by Charles C. Jain MD, Medical Resident, Massachusetts General Hospital

 

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?

What is the mechanism of pleural fluid formation in congestive heart failure (CHF)?

FA Manian MD, MPH, , Leave a comment

The pleural fluid in CHF originates from increase filtration of plasma across the capillaries of the visceral pleura and, more importantly, excess fluid in the interstitial spaces of the lung, both related to the increased hydrostatic and capillary wedge pressures (1).

It is postulated that leak of edema fluid into the pleural space may serve as a “safety valve” to mitigate overflooding of alveoli (2). 

Interestingly, although the pleural effusion is commonly bilateral in CHF, when unilateral, it is more likely on the right (1). The reason for this finding is unclear but several hypotheses have been put forth including compression of the azygous vein (which drains a portion of the parietal pleura of right lung) due to the dilatation of the right heart, and compression of the right pulmonary veins by an enlarged right atrium (1).  

Bonus Pearl: A minimum of 50 ml and 200 ml of pleural fluid are required for visibility on lateral and posteroanterior views of a chest radiograph, respectively (3).

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References

  1. Natanzon A, Kronzon I. Pericardial and pleural effusions in congestive heart failure—anatomical, pathophysiologic, and clinical considerations. Am J Med Sci 2009;338:211-216. https://www.ncbi.nlm.nih.gov/pubmed/19574887
  2. Zocchi L. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J 2002;20:1545-1558. http://erj.ersjournals.com/content/20/6/1545.short
  3. Mammarappallil JG, Anderson SA, Danelson KA, et al. Estimation of pleural fluid volumes on chest radiography using computed tomography volumetric analysis: an update of the visual prediction rule. J Thorac Imaging 2015;30:336-339.https://www.ncbi.nlm.nih.gov/pubmed/25811356

 

What is the mechanism of pleural fluid formation in congestive heart failure (CHF)?

What is the utility of pulmonary auscultation for crackles (rales) in diagnosing congestive heart failure (CHF) or pneumonia?

FA Manian MD, MPH, , , , , , 1 Comment

The evidence for the accuracy of crackles in CHF is not as robust as often assumed, with wide variations in its sensitivity (13%-70%), specificity (35%-100%), positive predictive value (19%-100%), and negative predictive value (17%-85%) (1).

In a study  of patients at high risk for CHF but without valvular heart disease, symptoms of CHF, or comorbid pulmonary disease,  the prevalence of baseline crackles in one or both lungs increased with age: 45-64 y , 11%; 65-79 y, 34%; and 80-95 y, 70%.  At best, fair or poor positive and negative likelihood ratios (LRs) have been reported for crackles in CHF (3.4, and 0.8, respectively) (2). 

The accuracy of crackles in diagnosing pneumonia in patients with cough and fever is not much better: sensitivity 19-67%, specificity 36-94%, and poor positive and negative LRs (1.8 and 0.8, respectively) (2).

So don’t overestimate the accuracy of crackles in CHF or pneumonia, especially if your suspicion for these conditions is high!

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References

  1. Kataoka H, Matsuno O. Age-related pulmonary crackles (rales) in asymptomatic cardiovascular patients. Ann Fam Med 2008;6:239-245.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2384982/ 
  2. McGee S. Auscultation of the lungs. In Evidence-based physical diagnosis (3rd ed.). Elsevier Saunders, Philadelphia, 2012.
What is the utility of pulmonary auscultation for crackles (rales) in diagnosing congestive heart failure (CHF) or pneumonia?

How should I interpret an isolated elevated hemidiaphragm on chest x-ray?

FA Manian MD, MPH, , Leave a comment

In hospitalized patients, an elevated hemidiaphragm on chest x-ray is not a rare finding and is frequently asymptomatic. It has many potential causes, including lobar collapse or surgical resection of the lung, diaphragmatic eventration, distention of stomach or colon, or phrenic nerve paralysis (1).  

Among patients with a paralyzed hemidiaphragm, damage to the phrenic nerve caused by surgery (e.g. cardiac), mediastinal tumors, cervical spine pathology, diabetes, autoimmune (e.g. vasculitis) and infectious causes (e.g. herpes zoster and polio viruses) are often cited as potential causes; most may be idiopathic, however (1,2,3).

Chest x-ray has a high negative predictive value (93%) but a poor positive predictive value for diagnosis of hemidiaphragm paralysis (1).  When in doubt, the fluoroscopic “sniff” test should be used for confirmation.  

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1. Chetta A, Rehman AK, Moxham J, et al. Chest radiography cannot predict diaphragm function. Resp Med 2005;99:39-44

2. Curtis J, Nawarawong W, Walls J, et al. Elevated hemidiaphragm after cardiac operations: incidence, prognosis, and relationship to the use of topical ice slush. Annals of Thoracic Surgery 1989;48:764-8.

3. Crausman RS, Summerhill EM, McCool FD. Idiopathic diaphragmatic paralysis: Bell’s palsy of the diaphragm? Lung 2009;187:153-157.

Contributed by Ethan Balgley, Harvard Medical Student

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How should I interpret an isolated elevated hemidiaphragm on chest x-ray?

Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?

FA Manian MD, MPH, , , Leave a comment

Although cachexia , a loss of >5% body weight over 12 months,  has been reported in about 30% of patients with cancer, many other chronic conditions  commonly encountered in our hospitalized patients may also be a culprit.  In fact, cachexia is not infrequent in CHF (20%), COPD (20%), kidney failure (40%), or rheumatoid arthritis (10%) (1,2).  We also shouldn’t overlook HIV and tuberculosis as a cause.

Cachexia is a multifactorial disease which does not fully reverse with nutritional support.  Numerous mediators have been implicated, including cytokines such as tumor-necrosis factor-α, and interleukin [IL]-1 and -6, as well as transforming growth factors such as myostatin and activin A (2). 

In patients with CHF, angiotensin II appears to be a key mediator, associated with insulin resistance, depletion of  ATP in skeletal muscles, poor appetite, reduction in insulin-like growth factor-1 (IGF-1), and an increase in glucocorticoid and IL-6 levels.  All these factors contribute to “cardiac cachexia” through muscle wasting, reduced food intake and lower muscle regeneration. 

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References

  1. Morely JE, Thomas DR, Wilson M-M G. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 2006;83:735-43. https://www.ncbi.nlm.nih.gov/pubmed/16600922
  2. Yoshida T, Delafontaine P. Mechanisms of cachexia in chronic disease states. Am J Med Sci 2015;35:250-256. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587350/
Besides malignancy, what other causes of cachexia should we usually consider in our hospitalized patients?

Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?

FA Manian MD, MPH, , , , , , , , , Leave a comment

Although we often think of syncope caused by acute pulmonary embolism (APE) in the setting of submassive or massive APE and right ventricular failure or shock (1,2), less massive APE may potentially cause syncope as well by triggering a vaso-vagal reflex (3).

For sure, a significant association between submassive or massive APE and syncope has been reported (1,2).  More specifically, patients with syncope and APE may be more likely to have systolic blood pressure <90 mmHg, right ventricular dilation and right ventricular hypokinesis (1). Another study reported a higher rate of central embolism (83% vs 43%), right ventricular dysfunction (91% vs 68%) and troponin positivity (80% vs 39%), but not 30 day mortality (2).

In contrast, 1 study found that patients with syncope as a presenting symptom of APE did not show a more serious clinical picture (e.g. shock) than those without syncope (3), while another found EKG signs of acute right ventricle overload in only 25% of patients with syncope (4).  

So while massive APEs may be associated with syncope, they don’t seem to be a prerequisite for this condition.

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References

1.  Omar HR, Mirsaeidi M, Weinstock MB, et al. Syncope on presentation is a surrogate for submassive and massive acute pulmonary embolism. Am J Emerg Med 2018;36:297-300. https://www.ncbi.nlm.nih.gov/pubmed/29146419

2. Altinsoy B, Erboy F, Tanriverdi H, et al. Syncope as a presentation of acute pulmonary embolism. Ther Clin Risk Manag 2016;12:1023-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930221/

3. Castelli R, Tarsia P, Tantardini G et al. Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope. Vascular Medicine 2003;8:257-261. https://journals.sagepub.com/doi/abs/10.1191/1358863x03vm510oa

4. Miniati M, Cenci, Monti S, et al. Clinical presentation of acute pulmonary embolism: survey of 800 cases. PloS One 2012;7:e30891.

 

 

Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?

What new treatment options are available for my patient with cystic fibrosis (CF) who has had recurrent pulmonary exacerbations requiring frequent hospitalizations?

FA Manian MD, MPH, , Leave a comment

CF is caused by gene mutations that result in deficient or dysfunctional transmembrane conductance regulator (CFTR) protein, an anion channel that is normally present in the epithelial membrane. Two FDA- approved drugs may provide new options for at least some CF patients. Ivacaftor (Kalydeco) is a CFTR protein potentiator that increases the probability that the CFTR channels are open in vitro and improves clinical outcomes in patients ≥12 years of age with at least one copy of G551D mutation, present in ~5% of CF patients (1). 

Orkambi is a combination of ivacaftor and lumacaftor – a drug that prevents intracellular destruction of CFTR –for patients with the Phe508del CFTR mutation, present in ~50% of CF patients.   Its use has been associated with fewer pulmonary exacerbations and hospitalization in patients (≥ 6 years of age) homozygous for this gene (2). Ivacaftor and Orkambi are priced at over $300,000/year and $295,000/year, respectively (http://www.nytimes.com/2015/07/03/business/orkambi-a-new-cystic-fibrosis-drug-wins-fda-approval.html?_r=0).

1. Ramsey BW, Davies J, McElvaney NG, et al. A CFTR Potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365:1663-1672.

2. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015;373:220-231.

Contributed by Cynthia M. Cooper, MD, Boston, MA

What new treatment options are available for my patient with cystic fibrosis (CF) who has had recurrent pulmonary exacerbations requiring frequent hospitalizations?