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Pulmonary

Last 50 Pulmonary Postings

(Click on title to be directed to posting, most recent listed first, CME offerings in Bold)

August 2016 Pulmonary Case of the Month
July 2016 Pulmonary Case of the Month
June 2016 Pulmonary Case of the Month
May 2016 Pulmonary Case of the Month
April 2016 Pulmonary Case of the Month
Pulmonary Embolism and Pulmonary Hypertension in the Setting of
   Negative Computed Tomography
March 2016 Pulmonary Case of the Month
February 2016 Pulmonary Case of the Month
January 2016 Pulmonary Case of the Month
Interval Development of Multiple Sub-Segmental Pulmonary Embolism in
   Mycoplasma Pneumoniae Bronchiolitis and Pneumonia
December 2015 Pulmonary Case of the Month
November 2015 Pulmonary Case of the Month
Why Chronic Constipation May be Harmful to Your Lungs
Traumatic Hemoptysis Complicating Pulmonary Amyloidosis
Staphylococcus aureus Sternal Osteomyelitis: a Rare Cause of Chest Pain
Safety and Complications of Bronchoscopy in an Adult Intensive Care Unit
October 2015 Pulmonary Case of the Month: I've Heard of Katy
   Perry
Pulmonary Hantavirus Syndrome: Case Report and Brief Review
September 2015 Pulmonary Case of the Month: Holy Smoke
August 2015 Pulmonary Case of the Month: Holy Sheep
Reducing Readmissions after a COPD Exacerbation: A Brief Review
July 2015 Pulmonary Case of the Month: A Crazy Case
June 2015 Pulmonary Case of the Month: Collapse of the Left Upper
   Lobe
Lung Herniation: An Unusual Cause of Chest Pain
Valley Fever (Coccidioidomycosis): Tutorial for Primary Care Professionals
Common Mistakes in Managing Pulmonary Coccidioidomycosis
May 2015 Pulmonary Case of the Month: Pneumonia with a Rash
April 2015 Pulmonary Case of the Month: Get Down
March 2015 Pulmonary Case of the Month: Sticks and Stones May
   Break My Bronchi
Systemic Lupus Erythematosus Presenting As Cryptogenic Organizing 
   Pneumonia: Case Report
February 2015 Pulmonary Case of the Month: Severe Asthma
January 2015 Pulmonary Case of the Month: More Red Wine, Every
   Time
December 2014 Pulmonary Case of the Month: Bronchiolitis in Adults
November 2014 Pulmonary Case of the Month: BAL Eosinophilia
How Does Genetics Influence Valley Fever? Research Underway Now To
   Answer This Question
October 2014 Pulmonary Case of the Month: A Big Clot
September 2014 Pulmonary Case of the Month: A Case for Biblical
   Scholars
Role of Endobronchial Ultrasound in the Diagnosis and Management of
Bronchogenic Cysts: Two Case Descriptions and Literature Review
Azathioprine Associated Acute Respiratory Distress Syndrome: Case Report
   and Literature Review
August 2014 Pulmonary Case of the Month: A Physician's Job is 
   Never Done
July 2014 Pulmonary Case of the Month: Where Did It Come From?
June 2014 Pulmonary Case of the Month: "Petrified"
May 2014 Pulmonary Case of the Month: Stress Relief
Giant Cell Myocarditis: A Case Report and Review of the Literature
April 2014 Pulmonary Case of the Month: DIP-What?
Wireless Capsule Endo Bronchoscopy
Elevated Tumor Markers In Coccidioidomycosis of the Female Genital Tract

 

For complete pulmonary listings click here.

The Southwest Journal of Pulmonary and Critical Care publishes articles broadly related to pulmonary medicine including thoracic surgery, transplantation, airways disease, pediatric pulmonology, anesthesiolgy, pharmacology, nursing  and more. Manuscripts may be either basic or clinical original investigations or review articles. Potential authors of review articles are encouraged to contact the editors before submission, however, unsolicited review articles will be considered.

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Friday
Jul032015

Reducing Readmissions after a COPD Exacerbation: A Brief Review

Richard A. Robbins, MD1

Lewis J. Wesselius, MD2

 

1The Phoenix Pulmonary and Critical Care Research and Education Foundation

Gilbert, AZ

2Mayo Clinic Arizona

Scottsdale, AZ

 

Abstract

CMS' Hospital Readmissions Reduction Program (HRRP) was extended to chronic obstructive pulmonary disease (COPD) exacerbations in October 2014. HRRP penalizes hospitals if admissions for COPD exacerbations exceed a higher than expected all-cause 30-day readmission rate. Recently, a review of 191,698 Medicare readmissions after a COPD exacerbation reported that COPD explained only 27.6% of all readmissions. Patients were more likely to be readmitted if they were discharged home without home care, dually enrolled in Medicare and Medicaid, and had more comorbidities (p<0.001 compared to patients not readmitted). Data on interventions is limited but recently a study of bundled interventions of smoking cessation counseling, screening for gastroesophageal reflux disease and depression or anxiety, standardized inhaler education, and a 48-h postdischarge telephone call did not result in a lower readmission rate. We conclude that there is limited evidence available on readmission risk factors, reasons for readmission and interventions that might reduce readmissions. In the absence of defined, validated interventions it seems likely that CMS's HRRP will be unsuccessful in reducing hospital readmissions after a COPD exacerbation.

Introduction 

To address rising costs and quality concerns, the Hospital Readmissions Reduction Program (HRRP) was enacted, targeting inpatient discharges in the Medicare fee-for-service population for congestive heart failure (CHF), acute myocardial infarction (AMI), and pneumonia in 2012. HRRP was extended to chronic obstructive pulmonary disease (COPD) exacerbations in October 2014.

Correlation of Readmissions with Outcomes

There were about 800,000 hospitalizations for COPD exacerbations annually, with about 20% of patients needing to be rehospitalized within 30 days of discharge (2,3). The cost of readmissions is about $325 million for the U.S. Centers for Medicare and Medicaid Services (CMS) (4). Therefore, it is hardly surprising that CMS is attempting to reduce COPD readmission to reduce costs. The implication is that care was incomplete or sloppy on the first admission, and that better care might reduce readmissions.

However, a number of concerns have been raised questioning the wisdom of the HRRP. Hospitals with better mortality rates for heart attacks, heart failure and pneumonia had significantly greater penalties for readmission rates (5). If this correlation is found to be true with randomized trials, then CMS is financially encouraging hospitals to perform an action with potential patient harm and suggest that CMS continues to rely on surrogate markers that have little or no correlation with patient-centered outcomes. Until this question is resolved, we cannot recommend programs that discourage hospital readmissions.

Differences between COPD Exacerbations and CHF, AMI and Pneumonia Methodology

Several aspects of COPD exacerbations differentiate it from other conditions included in HRRP. AMI, CHF, pneumonia and COPD exacerbations are all defined by discharge ICD-9 codes. Examination of ICD-9 coding against physician chart review found profound underestimation of COPD exacerbations, with sensitivities ranging from 12% to 25% and positive predictive values as low as 81.5% (6). In contrast, coding data to identify pneumonia and AMI have a sensitivity and positive predictive value of over 95% (7,8). Therefore, there is a high probability of misclassification of COPD exacerbations used to calculate the readmissions penalty.

COPD exacerbations are clinically defined while AMI and CHF are defined by biomarkers (plasma troponin, B-type natriuretic peptide) and pneumonia is defined by not only a compatible clinical situation but by consolidation on chest radiography. Because COPD symptoms overlap with many other diseases, biomarker and radiograph evidence can make accurate diagnosis difficult. Furthermore, this uncertainty in diagnosis may provide an opportunity for hospitals to game the system by excluding sicker patients who present with COPD from the readmission measure (9).

COPD may also require prolonged times for recovery as opposed to AMI, CHF, and pneumonia patients who seem to require shorter recovery times. One quarter of patients with a COPD exacerbation had not returned to preexacerbation peak expiratory flow rate by day 35 (10).

There is also a suggestion of a frequent exacerbation phenotype of COPD independent of disease severity (11). The single best predictor of exacerbations was a history of exacerbations, although a history of gastroesophageal reflux (GERD) was also associated with increased exacerbations. A hospital with higher numbers of patients with the frequent exacerbation phenotype or with GERD would be expected to have a higher readmission rate but would be penalized under CMS' HRRP.

Causes for Readmission after a COPD Exacerbation

Most patients readmitted after a COPD exacerbation are not readmitted for COPD. Shah et al. (9) recently examined nearly 200,000 COPD exacerbation hospital readmissions in the Medicare population. Only 27.6% were classified as being readmitted for COPD. There were a variety of readmission diagnosis with respiratory failure, pneumonia, CHF, asthma, septicemia, cardiac dysrhythmias, fluid and electrolyte disorders, intestinal infection, and non-specific chest pain and other accounting for the rest. This data is consistent with previous studies by Jencks et al. (12) who found 36.2% of exacerbation patients were readmitted for COPD. Not surprisingly, the sickest patients (as defined by the Charlson sum) are more likely to be readmitted (9). This would also be consistent with causes of readmission being diverse rather than limited to COPD.

Importantly, two observations were made which may have major implications for care after COPD exacerbations (9). First, patients dually enrolled in Medicare and Medicaid had higher readmission rates. These patients tend to be poorer and seek care at "safety net" hospitals. A penalty for readmissions would be largest at these hospitals which may most in need of financial help. Second, patients discharged home without home care were more likely to be readmitted. This will likely influence more discharges to either an extended care facility or with home care which may actually increase costs rather than result in the cost savings that CMS hopes to collect.

Interventions that Reduce COPD Readmissions

Jennings et al. (13) used a "bundle" for patients with COPD exacerbations in hopes of reducing readmissions and emergency department visits. The bundle consisted of smoking cessation counseling, screening for gastroesophageal reflux disease and depression or anxiety, standardized inhaler education, and a 48 hour postdischarge telephone call. It is easy to criticize these interventions. A single session of smoking cessation counseling is usually inadequate (14). Although gastroesophageal reflux disease has been associated with COPD, there is only a single trial with lansoprazole demonstrating a reduction in COPD exacerbations (15). To our knowledge there is no data on screening for depression or anxiety, standardized inhaler education and a single phone call in preventing COPD readmissions. Not surprisingly, the bundle did not work. However, it underscores that interventions to prevent COPD readmissions are unknown. Until these are defined, it seems unlikely that any program will be successful in reducing COPD readmissions.

Potential COPD Readmission Reduction Strategies

Discharge and Follow-Up

Discharge to an extended care facility or with home care reduces readmissions (9). Approximately one third of readmissions after hospitalization for COPD occur within 7 days of discharge and 60% occur within 15 days (9). Therefore, even close outpatient followup within 2 weeks of discharge from the hospital, may not prevent a majority of readmissions. However, we would recommend that close follow-up of patients be liberal which seems likely to have some impact on readmissions. Follow-up telephone calls may be reasonable but probably need to be more than a single call at 48 hours (13). We offer some additional suggestions below that have not been subjected to randomized trials, but seem reasonable based on the current state of knowledge.

Pharmacologic Therapy

  1. Bronchodilators. Many of the therapies that treat COPD exacerbations have been tested to determine if chronic use might prevent exacerbations. The best evidence is for the long-acting bronchodilators. Two large randomized controlled trials have confirmed that a combination of a long-acting beta agonist (salmeterol) with an inhaled corticosteroid (fluticasone) or a long-acting anticholinergic (tiotropium) reduce exacerbations (16,17). Given that only about one-third of readmissions are due to COPD, the impact, if any, with addition of long-acting bronchodilators after a COPD exacerbation would likely be small. The newer long-acting beta agonists and anticholinergics would also be expected to reduce exacerbations and might prevent readmissions.
  2. Inhaled corticosteroids. Addition of inhaled corticosteroids to long-acting bronchodilators in COPD remains controversial. A meta-analysis by Spencer et al. (18) recommended regular inhaled corticosteroid therapy as an adjunct in patients experiencing frequent exacerbations. However, the data supporting this recommendation is unclear. It is also unclear if their addition would prevent readmissions.
  3. Antibiotics. Continuous or intermittent treatment with some antibiotics, particularly macrolides, reduces exacerbations. Treatment with azithromycin for one year lowered exacerbations by 27% (19). Although the mechanism(s) accounting for the reduction in exacerbations is unknown, current concepts suggest the reduction is likely secondary to the macrolides’ anti-inflammatory properties. However, concern has been raised about a very small, but significant, increase in QT prolongation and cardiovascular deaths with azithromycin (20). In addition, the recent trial with azithromycin raised the concern of hearing loss which occurred in 25% of patients treated with azithromycin compared to 20% of control (19). An alternative to the macrolides may be tetracyclines such as doxycycline, which also possess anti-inflammatory properties but do not lengthen QT intervals nor cause hearing loss (21). Similar to the long-acting bronchodilators, antibiotics might reduce readmissions, but since most readmissions are not due to COPD, the effect would likely be small.
  4. Medication Compliance. Poor compliance with inhaled therapies has been implicated as a factor contributing to COPD exacerbations (22). The role of COPD medication noncompliance has not been specifically assessed in hospital readmissions, although it seems likely to be a contributing factor. Socioeconomic factors influence medication compliance and could lead to greater readmission rates in hospitals caring for patients with limited financial and social resources. Poor compliance with COPD medications as well as medications for comorbid conditions may both be important as most readmissions are not due to COPD.

Conclusions

Prevention of COPD readmissions after a COPD exacerbation represents a challenge with no straight-forward strategies to reduce readmissions other than discharge to an extended care facility or home with home health. Readmissions come from heterogeneous causes but most are not due to COPD suggesting that comprehensive care for disorders other than just COPD is likely important.

References

  1. Centers for Medicare and Medicaid Services. Readmissions reduction program. Available at: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html (accessed 6/4/15).
  2. Wier LM, Elixhauser A, Pfuntner A, Au DH. . Overview of hospitalizations among patients with COPD, 2008: Statistical Brief #106. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville, MD: Agency for Health Care Policy and Research (US); 2006–2011 Feb. Available from: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb106.pdf (accessed 5/4/15)
  3. Elixhauser A, Au DH, Podulka J. . Readmissions for chronic obstructive pulmonary disease, 2008: Statistical Brief #121. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville, MD: Agency for Health Care Policy and Research (US); 2006–2011 Sep. Available from: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb121.pdf (accessed 6/4/15).
  4. Medicare Payment Advisory Commission (MEDPAC). Report to the Congress: promoting greater efficiency in Medicare, 2007.
  5. Robbins RA, Gerkin RD. Comparisons between Medicare mortality, morbidity, readmission and complications. Southwest J Pulm Crit Care. 2013;6(6):278-86.
  6. Stein BD, Bautista A, Schumock GT, Lee TA, Charbeneau JT, Lauderdale DS, Naureckas ET, Meltzer DO, Krishnan JA. The validity of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for identifying patients hospitalized for COPD exacerbations. Chest. 2012;141(1):87-93. [CrossRef] [PubMed]
  7. Skull SA, Andrews RM, Byrnes GB, et al. ICD-10 codes are a valid tool for identification of pneumonia in hospitalized patients aged ≥ 65 years. Epidemiol Infect. 2008;136(2):232-40. [CrossRef] [PubMed]
  8. Kiyota Y, Schneeweiss S, Glynn RJ, Cannuscio CC, Avorn J, Solomon DH. Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records. Am Heart J. 2004;148(1):99-104. [CrossRef] [PubMed]
  9. Shah T, Churpek MM, Coca Perraillon M, Konetzka RT. Understanding why patients with COPD get readmitted: a large national study to delineate the medicare population for the readmissions penalty expansion. Chest. 2015;147(5):1219-26. [CrossRef] [PubMed]
  10. Seemungal TA, Donaldson GC, Bhowmik A, Jeffries DJ, Wedzicha JA. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161(5):1608-13. [CrossRef] [PubMed]
  11. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363(12):1128-38. [CrossRef] [PubMed]
  12. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. N Engl J Med. 2009;360(14):1418-28. [CrossRef] [PubMed]
  13. Jennings JH, Thavarajah K, Mendez MP, Eichenhorn M, Kvale P, Yessayan L. Predischarge bundle for patients with acute exacerbations of COPD to reduce readmissions and ed visits: a randomized controlled trial. Chest. 2015;147(5):1227-34. [CrossRef] [PubMed]
  14. Rigotti NA, Munafo MR, Stead LF. Smoking cessation interventions for hospitalized smokers: A systematic review. Arch Intern Med. 2008;168:1950-60. [CrossRef] [PubMed]
  15. Sasaki T, Nakayama K, Yasuda H, Yoshida M, Asamura T, Ohrui T, Arai H, Araya J, Kuwano K, Yamaya M. A randomized, single-blind study of lansoprazole for the prevention of exacerbations of chronic obstructive pulmonary disease in older patients. J Am Geriatr Soc. 2009;57(8):1453-7. [CrossRef] [PubMed]
  16. Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J; TORCH investigators. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356:775-89. [CrossRef] [PubMed]
  17. Tashkin DP, Celli B, Senn S, Ferguson GT, Jenkins C, Jones PW, Yates JC, Vestbo J; TORCH investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359:1543-54. [CrossRef] [PubMed]
  18. Spencer S, Karner C, Cates CJ, Evans DJ. Inhaled corticosteroids versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD007033. [PubMed]
  19. Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR; COPD Clinical Research Network. COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011; 365:689-98. [CrossRef] [PubMed]
  20. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366:1881-90. [CrossRef] [PubMed]
  21. Rempe S, Hayden JM, Robbins RA, Hoyt JC. Tetracyclines and pulmonary inflammation. Endocr Metab Immune Disord Drug Targets. 2007;7:232-6. [CrossRef] [PubMed]
  22. Ismaila A, Corriveau D, Vaillancort J, Parsons D, Dalal A, Su Z, Sampalis JS. Impact of adherence to treatment with tiotropium and fluticasone propionate/salmeterol in chronic obstructive pulmonary disease patients. Curr Med Res Opin. 30(7);1427-36, 2014. [CrossRef] [PubMed] 

Reference as: Robbins RA, Wesselius LJ. Reducing readmissions after a COPD exacerbation: a brief review. Southwest J Pulm Crit Care. 2015;11(1):19-24. doi: http://dx.doi.org/10.13175/swjpcc089-15 PDF

Wednesday
Jul012015

July 2015 Pulmonary Case of the Month: A Crazy Case

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

 

History of Present Illness

A 23-year-old woman presented in 2008 at outside institution with dyspnea and diffuse pulmonary infiltrates. She required intubation. After a surgical lung biopsy, she was transferred to the Mayo Clinic Hospital for further care.

Past Medical History

She has had a history of progressive dyspnea for several months, otherwise negative 

Physical Examination

Vital signs are stable. SpO2 94% on FiO2 of 0.4. She is intubated and there is a chest tube in her right chest. Otherwise the physical examination is unremarkable.

Radiography

A thoracic CT scan was performed (Figure 1).

Figure 1. Representative images from the thoracic CT in lung windows.

Which of the following are present on the thoracic CT scan? (click on the correct answer to proceed to the second of five panels)

  1. Diffuse ground-glass opacities
  2. Interlobular septal thickening and intralobular reticular thickening
  3. Right-sided pneumothorax
  4. 1 and 3
  5. All of the above

Reference as: Wesselius LJ. July 2015 pulmonary case of the month: a crazy case. Southwest J Pulm Crit Care. 2015;11(1):3-10. doi: http://dx.doi.org/10.13175/swjpcc079-15 PDF

Monday
Jun012015

June 2015 Pulmonary Case of the Month: Collapse of the Left Upper Lobe

G. Zacharia Reagle DO

Andreas Escobar-Naranjo MD

 

Department of Internal Medicine

Division of Pulmonary and Critical Care

UCSF Fresno

Fresno, CA

  

History of Present Illness

A 65 year-old woman who recently quit smoking presented to the ER for the third time in the preceding month with dyspnea and cough. She reported some subjective fevers and cough productive of white sputum as well as a seven kilogram unintentional weight loss in the prior four to eight weeks. She had been diagnosed with COPD in the past and on both prior ER visits was treated with oral steroids and antibiotics. She would feel some relief with the steroids but once the course was over she would quickly experience a return of her symptoms. On the third ER presentation she was admitted to the hospital.

Past Medical History:

  • Asthma
  • HTN
  • Hypothyroidism

Past Surgical History:

  • C-section x 2
  • TAH and BTL
  • Appendectomy
  • Tonsillectomy

Medications:

  • Levothyroxine 0.15mg daily
  • Budesonide 40/formoterol 4.5 twice daily
  • Tiotropium 18 mcg daily
  • Fluoxetine 20mg daily
  • Hydroxyzine 50mg three times daily
  • Hydrochlorothiazide 50/triamterene 75 daily
  • As needed albuterol

Allergies: No Known Drug Allergies

Social History:

A lifelong Californian, she was divorced with two healthy adult children. She is a United States Air Force veteran who served as a broadcaster from 1974-78 including a deployment to Asia. After leaving the service she worked as a Registered Nurse in burn, rehab and home health nursing. A former tobacco smoker with 35+ pack years of tobacco exposure – she quit smoking one month prior to the current admission. She is currently homeless, living in a homeless veteran’s shelter. She is a recovering alcoholic and cannabis addict.

Physical Exam:

General: Alert, mild respiratory distress, mildly anxious.

Vitals: BP: 134/80 HR: 104 RR: 18, SpO2 93% on room air T: 98.4ºF

HEENT: NC/AT, PERRL, neck supple without JVD noted.

Lungs: equal chest expansion, scattered bilateral wheezes with decreased airflow on the left

Heart: Regular with a good S1 and S2, no murmurs or gallops were appreciated.

Abdomen soft, Non-tender, good bowel sounds.

Extremities No edema, nor clubbing.

Neurological: She was alert and oriented with a Glasgow Coma Score of 15, no focal defects noted.

Skin: No rashes noted.

Laboratory:

CBC: WBC 6.9 X 109 cells/L, hemoglobin13.4 g/dL, hematocrit 39.4, platelet count 329 X 109 cells/L

Chemistries: Na+ 139 mEq/L, K+ 3.5 mEq/L Cl- 106 mEq/L, CO2 26 mEq/L  BUN 8 mg/dL, creatinine 0.6 mg/dL, glucose 149 mg/dL, magnesium 2.0 mg/dL, phosphate 3.4 mg/dL

Mycoplasma IgM: (-)

S. pneumoniae urinary antigen: (-)

Legionella urinary antigen: (-)

Blood Cultures: (-)

Imaging:

On admission a chest CT was preformed (Figure 1).

Figure 1. Representative images from the thoracic CT scan showing central and upper zone predominate bronchiectasis, and total collapse of the left upper lobe. There also was some emphysema noted.

Which of the following causes of bronchiectasis should be considered in this case? (Click on the correct answer to proceed to the second of six panels)

  1. Allergic bronchopulmonary aspergillosis
  2. Autoimmune diseases including rheumatoid arthritis and Sjogren’s syndrome
  3. Congenital pulmonary conditions including cystic fibrosis and primary ciliary dyskinesia
  4. Immunoglobulin deficiency
  5. All of the above are possible causes of bronchiectasis

Reference as: Reagle GZ, Escobar-Naranjo A. June 2015 pulmonary case of the month: collapse of the left upper lobe. Southwest J Pulm Crit Care. 2015;10(6):315-22. doi: http://dx.doi.org/10.13175/swjpcc072-15 PDF 

Saturday
May302015

Lung Herniation: An Unusual Cause of Chest Pain

Max L. Cohen MD PhD

Sumugdha Rayamajhi MD

Jonathan S. Kurche MD PhD

Carolyn H. Welsh MD

 

Denver VA Medical Center

University of Colorado Denver

Denver, CO

 

Abstract

We report a morbidly obese 72-year-old man admitted with acute right-sided chest pain and hypoxemia following bouts of vigorous coughing. This case illustrates the need to consider unusual etiologies of a common clinical presentation.

Case Presentation

History of Present Illness

A 72-year-old morbidly obese male presented with a feeling of tearing chest pain radiating to the right flank following repeated bouts of vigorous coughing. He was unable to take in a deep breath or lie flat and developed an abdominal bruise shortly after the tearing pain. He denied fever, dizziness or change in his baseline clear phlegm.

His medical history included GOLD I chronic obstructive pulmonary disease for which he used daily inhaled budesonide/formoterol, as-needed inhaled albuterol/ipratropium, and supplemental oxygen with exertion at 3 liters per minute. One year prior to admission, his FEV1/FVC ratio was 0.69 with air trapping and diffusion capacity 79% predicted. He had severe obstructive sleep apnea with an apnea hypopnea index of 52 for which he used home bi-level positive pressure at night at 25/14 cm water (IPAP/EPAP) with supplemental oxygen at 2 liters per minute. He had not recently received systemic corticosteroids; his last course was 5 months prior to admission.

Past Medical History

He had hypertension, hypothyroidism, gout, an umbilical hernia, hyperlipidemia, diverticulosis, and a peripheral neuropathy due to Agent Orange exposure.

Past surgical history included a remote uvulopalatopharyngoplasty (UPPP) for his sleep apnea. Three years previously he fell from a motor scooter and was hospitalized with four fractured left ribs.

He drank alcohol frequently until several months prior to admission.

Physical Examination

Vital signs on presentation were significant for a heart rate of 110, a respiratory rate of 22, and hypoxia with an O2 saturation of 88% on room air. His BMI was 52 kg/m2. Breath sounds were distant and diminished on the right side. He had extensive ecchymosis extending from the right flank to the periumbilicum, and a tender right chest wall in the lower mid-clavicular region. He had a large umbilical hernia that was easily reduced. His legs showed 3+ edema to the thighs.

Laboratory findings

He had a white blood cell count of 11,300/ul, a hemoglobin of 10.9 g/dL, and a platelet count of 319,000/ul. He had a normal creatinine, electrolytes, and a negative troponin. The proBNP was 449 pg/ml.

Radiography

Admission roentography and computed tomography of the chest with contrast (not shown) initially revealed hyperinflated lungs, a small loculated pleural effusion, a chest wall hematoma on the right, and no pulmonary thromboembolus.

Hospital Course

Bi-level positive pressure non-invasive ventilation (PAP) was resumed with his normal home settings of 25/14 cm water. Supplemental oxygen was administered, and a combination of opiates and NSAIDs were used for pain control. He remained hypoxic, with a persistent cough, and worsening pain. The character of the pain changed from tearing to pleuritic. Repeat computed tomography of the chest prompted by persistent pain revealed herniation of lung parenchyma through the 8th and 9th rib to the extrathoracic space (Figures 1).

Figure 1. Panel A: Repeat CT scan with axial reconstruction demonstrating extra-thoracic presence of lung parenchyma (arrow). Panel B: Repeat CT scan with coronal reconstruction demonstrating herniation of lung parenchyme through the 8th-9th intercostal space (arrow).

A palpable subcutaneous mass was not present at any point during his hospitalization. The cardiothoracic surgery service was consulted for possible intervention. Given the non-incarcerated nature of hernia and presence of multiple comorbidities, a decision was made to conservatively manage and follow with repeated thoracic imaging. His pain and hypoxemia gradually improved.

Six months after presentation, lung herniation was still visible on roentography (Figure 2) but he had minimal residual pain.

Figure 2. PA chest film 6 months after initial presentation showing persistence of herniated lung (arrow).

Due to the lack of symptoms, no surgical intervention was recommended.

Discussion

Pulmonary herniation is rare. By definition, it is the protrusion of lung tissue and pleural membranes beyond the confines of thoracic cavity, and is classified as Cervical, Thoracic, Diaphragmatic or Mediastinal depending on its anatomic location (1). Etiology-based classification divides it as congenital or acquired; while congenital hernias are typically found early in life, they can present in adults (2).  Congenital hernias are associated with costal or cartilage malformation, whereas acquired hernias involve intercostal muscle weakness, especially with conditions that cause increases in intrathoracic pressure such as coughing (3), heavy weight lifting, profound obesity, or positive-pressure ventilation (including by non-invasive methods) (1-4). Other precipitating factors can include trauma, surgery, chronic obstructive pulmonary disease, asthma, chronic steroid use, inflammatory or neoplastic process (1-5). Our patient had many of the known above-mentioned risk factors and developed spontaneous traumatic herniation, likely due to vigorous coughing that led to an intercostal muscle tear. While rare, lung herniation should be considered in a patient with risk factors and chest pain, dyspnea, or hypoxemia without a clear cause.

References

  1. Detorakis E, Androulidakis E. Intercostal lung herniation--the role of imaging. J Radiol Case Rep. 2014;1(8):16–24. [CrossRef] [PubMed]
  2. Weissberg D, Refaely Y. Hernia of the lung. Ann Thorac Surg. 2002;74(6):1963-6. [CrossRef] [PubMed]
  3. O'Shea M, Cleasby M. Lung herniation after cough-induced rupture of intercostal muscle. N Engl J Med. 2012;366(1):74. [CrossRef] [PubMed]
  4. Sulaiman A, Cottin V, De Souza Neto EP, Orsini A, Cordier JF, Gamondes JP, Tronc F. Cough-induced intercostal lung herniation requiring surgery: Report of a case. Surg Today. 2006;36(11):978–80. [CrossRef] [PubMed]
  5. Cafarotti S, Matarelli E, Guerra A, Dutly A. Large intercostal pulmonary hernia secondary to limited-access aortic valve surgery: video-assisted thoracoscopic technique repair. Lung. 2013;192(2):333–4. [CrossRef] [PubMed]

Reference as: Cohen ML, Rayamajhi S, Kurche JS, Welsh CH. Lung herniation: An ususal cause of chest pain. Southwest J Pulm Crit Care. 2015;10(5):311-4. doi: http://dx.doi.org/10.13175/swjpcc060-15 PDF

Monday
May182015

Valley Fever (Coccidioidomycosis): Tutorial for Primary Care Professionals

John N. Galgiani, MD

 

Valley Fever Center For Excellence

The University of Arizona

Tucson, AZ

 

Preface

In the south and central deserts of Arizona and the central valley of California, Valley Fever should be a familiar phrase to clinicians and patients alike. It is estimated that over 50,000 persons each year, or approximately 1% of the population within the most endemic regions, seek medical care for newly acquired Valley Fever infections. Certain medical and surgical specialists practicing in these areas are particularly likely to be aware of the less frequent but more serious complications of the disease. In recent years, both the Centers for Disease Control and Prevention and the Arizona Department of Health Services have contributed significantly to our understanding of Valley Fever as a public health problem.

However, despite the significant impact of these complications on regional public health and individual lives, the majority of these infections are managed by primary care clinicians either without an accurate diagnosis or with sub-optimal care.

In January 1996, the Valley Fever Center for Excellence established a hotline that physicians and others with questions about Valley Fever could call for information. From the questions received through the hotline, it became increasingly apparent that many details about the causes of and necessary responses to Valley Fever were not fully understood.

One area of particular importance was the need for timely diagnosis and proper management of the initial respiratory infection. Early diagnosis of Valley Fever by primary care professionals can improve patient care by reducing patient anxiety, unneeded diagnostic tests, and unwarranted use of antibacterial agents. Moreover, early appropriate treatment can reduce the incidence of serious complications requiring additional treatment. We hope to improve this situation with this revised edition of Valley Fever (Coccidioidomycosis) Tutorial for Primary Care Professionals.

The purposes of this monograph are two-fold. First, it is intended to be a  syllabus to accompany a medical education program on the primary care aspects of coccidioidomycosis organized by the Valley Fever Center for Excellence. Slide presentations from the CME program can be found at the  Valley Fever Center for Excellence website (www.vfce.arizona.edu). While this syllabus does not follow the presentation structure of the CME program, it covers much of the same information. 

Medical centers, health maintenance organizations, or other medical groups interested in bringing this program to their site for their clinicians can arrange to do so by contacting the Center at (520) 626-6517 or through its website at http://www.vfce.arizona.edu.

Second, this publication is designed to be a reference for the office shelf. The information it contains is not intended to be an exhaustive review of the disease. The content was selected for its relevance and usefulness to busy family practitioners, internists, emergency room personnel, and others dealing with patients in the primary care setting, especially within regions endemic for the Coccidioides species.

We hope you find this information helpful. Formatting and printing of this version of Valley Fever (Coccidioidomycosis) Tutorial for Primary Care Professionals was made possible by an unrestricted grant to the Valley Fever Center for Excellence from Nielsen BioSciences, whose support we greatly appreciate.

Overview  of Coccidioidomycosis

History

The first patient recognized with what is now known as coccidioidomycosis was an Argentinean soldier in 1893. The first North American patient was recognized by a San Francisco surgeon the following year. First thought to be a protozoan infection, its true fungal nature was determined in 1900.

Initially, the infection was considered rare and fatal, but that understanding has changed dramatically. By 1935, it had been linked to the common illness known as San Joaquin Valley Fever and by the 1940s, its existence within southern Arizona was well appreciated. In addition, it is now recognized to present in a range of severities, and most people that contract the disease are known to become immune to it after a single infection (Table 1).

Table 1. Valley Fever at a Glance

Mycology

The fungal species that cause Valley Fever are in the genus Coccidioides: C. immitis and C. posadasii. In the past, all strains were designated as C. immitis, but recent genetic analysis has shown that strains segregate into two distinct groups. Strains now designated C. immitis in most cases originate from infections contracted in California. Those designated C. posadasii are from infections contracted elsewhere. At the present time, most clinical laboratories do not determine species for new isolates. Therefore, the simple case designation Coccidioides spp. is technically accurate.

In the soil (Figure 1), Coccidioides spp. survive as mycelia, growing beneath the surface at a depth ranging from inches to a few feet.

Figure 1. The life cycle of Coccidioides spp.

Since the fungus is an obligate aerobe, oxygen content is a major factor limiting the depth that it can survive in the dirt. During rainy periods, mycelia proliferate and grow closer to the surface. When the rains cease and the ground dries, the mycelia stop elongating. Along their length, alternating cells undergo autolysis, lose their internal contents, and their walls become extremely brittle. The remaining barrel-shaped single cells (known as arthroconidia) are then easily disrupted.

The size of each arthroconidium is approximately 3-5 μm. This is small enough to both remain suspended in the air and be inhaled deep into the lungs, thereby establishing an infection. At that point, an arthroconidium transforms into a spherical shape and enlarges, frequently to as much as 75 μm in diameter. Inside the growing spherule, the cell wall invaginates to repeatedly transect the space, dividing into many scores of subcompartments, each containing viable cells, termed endospores. In active infections, a mature spherule ruptures its outer wall and releases the endospore progeny, each of which can develop into another spherule. If specimens containing spherules are cultured in a laboratory, growth reverts to the mycelial form.

Epidemiology

The endemic regions of Coccidioides spp. roughly correspond to the “lower Sonoran life zone” and are areas of low rainfall, high summer temperatures, and moderate winter temperatures. Regions that fit that description are found in the

southern deserts of Arizona (including Maricopa, Pinal, and Pima counties), the central valley and southern portions of California (including Kern, Tulare, and San Luis Obispo counties), the southern tip of Nevada, southern Utah, southern New Mexico, western Texas (especially along the Rio Grande), and the northern and Pacific coastal areas of Mexico. Recently, a pocket of Coccidioides has been identified in Washington State. Some areas have been identified in Central and South America as well (Figure 2).

Figure 2. Shaded areas indicate suspected coccidioidomycosis distribution in the Western Hemisphere.

Even within endemic regions, the distribution in the soil is not uniform, and, in fact, most acreage appears free of the fungus. Thus, while occasionally disruption of soil produces increased risk of exposure, such activity often does not. Conversely, windy conditions, which typically involve large areas of the desert, may more likely result in arthroconidia becoming airborne and distributed across urban and rural areas alike. The implication is that exposure to Coccidioides spp. is more associated with living in or visiting endemic areas per se than it is with engaging in activities associated with heavy dust exposure.

Since infection occurs after inhaling an arthroconidium that has developed in the soil, virtually all infections originate in an endemic region. Very rarely, dirt which contains arthroconidia carried from the endemic region has been the source of infection elsewhere. It’s important to note that infection resulting from respiratory exposure to an infected patient has never been reported, and patients with Valley Fever need not be isolated from others. Peak infection rates occur during the driest periods of the year. In Arizona, this is the early summer and late fall, whereas in California, it is all throughout the summer.

Spectrum of Disease

The majority of infected persons have symptoms so mild that they see no need for medical attention. Of the approximately one-third of infected persons who do suffer a clinical illness, the symptoms are primarily those suggesting community-acquired pneumonia. For most such patients, it is not possible without specific laboratory testing to distinguish Valley Fever pneumonia from that caused by other etiological agents.

Whether diagnosed or not, most infections are controlled by induction of immunity, although the associated illness may last for many weeks to many months. Approximately 5% to 10% of infections result in pulmonary sequelae, and 1% or less result in the spread of the infection outside of the lungs. This leads to destructive lesions in the skin, bones, joints, meninges, and virtually any other organ or tissue in the body to which the infection has spread. These complications produce a large amount of chronic morbidity and cause an average of fewer than 200 deaths annually in the United States (Table 2).

Table 2. Spectrum of Coccidioidomycosis

Current Therapies

Many patients with Valley Fever pneumonia require no treatment, and the illness resolves as a consequence of acquired immunity. However, in some patients, coccidioidal pneumonia is acute and very severe. In others, it produces various progressive pulmonary syndromes or leads to spread of infection to other parts of the body. Such complications dictate the need for treatment, and even so the infection may remain difficult to control.

A majority of complicated infections follow a subacute or chronic progression, and initial therapy usually involves oral administration of azole antifungals, such as fluconazole or itraconazole. Typically, treatment is continued for many months to years. When therapy is discontinued after the apparent successful control of disease, a relapse of infection occurs in approximately one-third of patients.

Therefore, some patients may need lifelong therapy to maintain control.  Chief among these are patients with deficiencies in cellular immunity or those with coccidioidal meningitis. Amphotericin B is effective only if administered parenterally, and its use is often associated with significant side effects and toxicities. Despite these drawbacks, in rapidly progressive infections, amphotericin B remains the preferred initial treatment.

The Importance of Valley Fever in Primary Care

Case Reporting

Coccidioidomycosis is a reportable disease at the national level, and reporting is required in Arizona and California where cases annually number in the thousands (Figure 3).

Figure 3. Annual number of cases of coccidioidomycosis reported in Arizona and California.

In addition, the fact that Arizona has approximately twice as many infections as California is related to the differences in the population sizes in the most intensely endemic regions of the two states (Table 3).

Table 3. Population (in millions) of Selected Counties in Regions Highly Endemic for Coccidioidomycosis.

In 2007, the Arizona Department of Health Services conducted a telephone survey of nearly 500 persons, approximately 10% of those reported being newly diagnosed with Valley Fever that year (1). From these interviews, it was found that more than half were ill for longer than six months, 75% were unable to do usual daily activities for longer than three months, and 75% of workers missed an average of one month of employment. Also found were significant delays  in diagnosis.

For example, patients waited 44 days before seeking care for their illness. Once care was sought, there was an additional average delay of five months involving three or more clinic visits before the correct diagnosis was made. The impact on the health care system was substantial since over half of patients sought their care from emergency rooms, 40% of those were hospitalized one or more nights, and 25% of the patients required 10 or more visits to clinicians to manage their illness. From Arizona hospital records, there were over 1700 admissions resulting from Valley Fever infections in 2012, costing over $100 million.

As significant as these findings are, other analyses indicate that compared with the number of reported infections, the number of undiagnosed infections is even more substantial. In one study conducted in Phoenix, only 2% to 13% of patients with community-acquired pneumonia were tested for Valley Fever (2). In contrast, when Tucson patients with a clinical diagnosis of community-acquired pneumonia were prospectively tested for Valley Fever, 29% were found to be positive (3).

These and other less direct measurements all indicate that approximately 50,000 patients annually seek medical care for Valley Fever pneumonia (4). Since most coccidioidal infections can only be diagnosed by specific laboratory testing, the lack of clinicians testing for Valley Fever could easily account for the under-reporting of illness by as much as 90%.

Undiagnosed infections are almost certainly not as serious as those that are recognized. Nonetheless, there are several very important reasons why diagnosis, especially in the primary care setting, should be pursued.

Value of Early Diagnosis

A primary reason for diagnosing early coccidioidal infections is simply that it provides patients with answers to why they are feeling so poorly. By giving an illness a specific name, it removes the patient’s fear of the unknown. Diagnosis has always been a major contribution by clinicians, and the value of diagnosis to patient satisfaction should not be underestimated.

This is especially true for older patients, where the concern exists that an undiagnosed respiratory illness may represent cancer. A myriad of physical, mental, and emotional consequences are associated with an incorrect or suspected diagnosis of cancer.

For patients of all ages, an accurate diagnosis allows for reassurance in most cases and appropriate prognostic patient education.

In addition, early diagnosis of Valley Fever reduces or eliminates the need to search for another diagnosis. The symptoms associated with Valley Fever that take weeks or even months to resolve often prompt concerned clinicians to subject their patients to diagnostic blood tests, chest X-rays, CT scans, PET scans, bronchoscopy, percutaneous fine-needle aspiration, and even thoracotomies. These procedures have attendant costs, discomfort, and potential complications, which might be avoided if coccidioidomycosis were known to have been responsible for the symptoms that patients experience.

A third benefit of diagnosing coccidioidal infections early is the reduction or elimination of empiric therapy for bacterial infection. Patients with persistent respiratory complaints often receive empiric antibiotics in an ambulatory practice.

In one study, 81% of patients with Valley Fever pneumonia received at least one course, and 31% received multiple courses of antibacterial treatment for their illness (3).

In addition to the cost of antibiotics, this strategy has the potential to cause adverse events for the patient and increase antibiotic resistance in the community. A less frequent but potentially more serious problem is the use of corticosteroids for the cutaneous or rheumatologic complaints that may accompany primary coccidioidal infection. The anti-inflammatory effects of corticosteroids may impede host defenses, and their use in patients with early coccidioidal infections may cause adverse effects.

Finally, by establishing a diagnosis of coccidioidomycosis early, complications (should they arise) may be more quickly recognized and treated. Complications of coccidioidal infection usually manifest within months of the initial infection.

For this reason, symptoms that are associated with or develop in the weeks following a new coccidioidal infection may indicate extrapulmonary spread. A more detailed evaluation of new symptoms at this stage may identify a need for treatment earlier and reduce tissue destruction and consequent morbidity (Table 4).

Table 4. The Value of Early Diagnosis

In summary, the attitude that primary care professionals take regarding early diagnosis of coccidioidal infections is critical to all further discussion about the proper management of this infection in the primary care setting. Historically, the approach in general has been passive, leaving diagnosis and treatment to only the most severely ill. Providing an accurate, early diagnosis can decrease patient anxiety and eliminate unwarranted diagnostic testing and unnecessary exposure to antibiotics. Also, it can allow for earlier identification and treatment of complications.

The Arizona Department of Health Services has recommended that physicians whose patients have endemic exposure to Valley Fever be tested for this possibility should they develop signs and symptoms of pneumonia. The Valley Fever Center for Excellence endorses that recommendation as reflected in this monograph. The following section, then, describes general strategies for primary care professionals to identify and manage this important disease.

Primary Care Management of Coccidioidomycosis

Overview

The following section outlines an approach for recognizing a new infection, assessing its impact on the patient, and subsequently managing the illness depending upon its level of complications. We have developed an acronym (COCCI) for this approach based on 5 important steps.

Spectrum of Clinical Manifestations of Valley Fever

Consider the Diagnosis

The incubation period of coccidioidal infection ranges from 7 to 21 days, after which a variety of manifestations develop. The most common symptoms are fatigue, night sweats, and pulmonary symptoms (cough, chest pain, dyspnea, and hemoptysis). Although difficult to quantify, fatigue is often the most prominent symptom. Stories like “I went to bed and didn’t wake up for 15 hours” or “I got up for breakfast and then was exhausted” are common.

When a cough is present, it frequently is not particularly productive of large amounts of sputum. Fever is present in nearly half of patients. A headache occurs in approximately one-fifth of the patients with early infection; fortunately, as a transient symptom, this does not represent meningitis. Weight loss of as much as 5% to 10% is also common with coccidioidal infections. It is apparent from this that the clinical presentation overlaps substantially with the presentation of many other types of respiratory illnesses.

Skin manifestations include a diffuse nonpruritic maculopapular eruption which has been noted to occur in 16% of males and 7% of females, especially children and young adults. It is so transient and seemingly inconsequential that it is often missed. More notable are erythema nodosum (seven to eight times more frequent in women than men) and erythema multiforme. These two rashes are not specific for coccidioidomycosis. However, when found in patients with endemic exposure to Coccidioides spp., Valley Fever is frequently responsible.

Another symptom is diffuse and migratory arthralgia, present in 22% of patients. Joints may be mildly inflamed and painful but typically do not exhibit an effusion. The triad of fever, erythema nodosum, and diffuse arthralgias has produced the synonym of “desert rheumatism” for the disease. All of these manifestations are thought to be immunologically mediated and not the consequence of viable fungal cells in either the skin or the joints.

Chest radiographs often, but not always, disclose abnormalities associated with the early infection. Pulmonary infiltrates are usually one-sided and are typically patchy and not as consolidated as seen with bacterial infections. Often there is associated ipsilateral hilar adenopathy. Peripneumonic pleural effusions may also occur as part of a primary infection. Although disease of one lung is the rule, the process can occasionally be bilateral (Table 5).

Table 5. The Clinical Manifestations of Valley Fever

Routine laboratory findings commonly do not show specific abnormalities. Peripheral blood leukocyte counts are usually normal or only slightly elevated. Eosinophilia is sometimes present and occasionally to strikingly high levels. Erythrocyte sedimentation rate and C-reactive protein are often elevated.

However, recent studies indicate that serum procalcitonin levels are usually normal, which may be a useful way to distinguish coccidioidal from bacterial pneumonia.

Attempts to use clinical presentation and routine laboratory results as an indicator of coccidioidal infection have been uniformly unsuccessful. In one study, several patient findings were significantly associated with coccidioidal infection, as compared to patients with other causes of acute respiratory problems (5). However, the predictive value of these abnormalities was very limited and not of practical help in identifying most infections.

Selecting Patients for Evaluation

Since the signs, symptoms, and routine laboratory abnormalities are nonspecific, virtually any patient evaluated for a variety of complaints, especially those related to the respiratory system, could arguably be evaluated for coccidioidomycosis. The more patients that are tested for Valley Fever, the more infections are likely to be diagnosed.

On the other hand, despite the prevalence of Valley Fever within the endemic patient population, many other acute illnesses also exist. Thus, by increasing provider sensitivity and the number of tests ordered to diagnose Valley Fever, the overall proportion of tests that are diagnostic will decrease.

A critical step for clinicians in a busy practice is to establish routine indications for ordering the appropriate tests. Several indications are proposed, which are selected for simplicity and application to common situations (Table 6).

Table 6. In patients who reside in or have traveled to endemic regions, consider testing for coccidioidomycosis if any of the following indications are present:

Order the Right Tests

Detection of Anticoccidioidal Antibodies in Serum: Serologic Tests

For diagnosing primary infections, serologic tests are the most commonly employed laboratory approach. Of the variety of tests available, some are highly specific for an active infection, while a few have a significant frequency of false- positive results.

Specific tests are typically selected by the director of the clinical laboratory. Factors involved in such selection include the cost and rapidity of obtaining results, the availability of tests from specific reference laboratories that provide other testing services, and the sensitivity and specificity of the tests. Moreover, tests available to a specific provider may change over time because of renegotiated contracts and other factors. This has complicated the interpretation of coccidioidal serologic testing. Because of this, the following two general principles are useful in the primary care setting:

First, in most circumstances, a positive serologic test for coccidioidal antibodies is highly presumptive of a current coccidioidal infection. Therefore, a report of a positive serologic test should always be reviewed by someone familiar with test interpretation. Second, a negative serologic test never excludes the presence  of a coccidioidal infection. For this reason, in evaluating a possible coccidioidal infection, one or even two repeated serologic tests will increase the sensitivity for diagnosis. If repeated testing over the course of two months fails to produce a serologic diagnosis, further serologic testing is likely to be unrewarding.

“A positive serologic test for coccidioidal antibodies is highly presumptive of a coccidioidal infection. Therefore, a positive serologic result should always be reviewed by someone familiar with test interpretation.”

“A negative serologic test should never exclude a coccidioidal infection. In evaluating a possible coccidioidal infection, repeated serologic tests will increase the sensitivity for diagnosis.”

Tube Precipitin (TP) Antibodies

Antibodies of this type were originally detected by the presence of a precipitin button that formed at the bottom of a test tube after overnight incubation of patient serum mixed with coccidioidal antigen. Because IgM is most adept at forming such immune precipitins and because these reactions were detected early after onset of infection, this test is now often referred to as the “IgM test.”

The antigen responsible for this reaction is a polysaccharide from the fungal cell wall. Up to 90% of patients will have TP antibodies detected at some time within the first three weeks of symptoms, and this will decline to less than 5% after seven months of the onset of a self-limited illness.

Complement Fixing (CF) Antibodies

When patient serum is mixed with coccidioidal antigen, an immune complex forms which consumes complement. This event is detected by the subsequent addition of tanned red blood cells, which normally lyse in the presence of complement but remain intact if the complement is depleted. Since IgG is the immunoglobulin class usually involved in such immune complexes, this test is often referred to as the “IgG test.”

Although this test was originally developed using various complex extracts of C. immitis, it is now known that the antigen involved in this reaction is a chitinase, a protein enzyme important in the structure of the fungal cell wall. In early coccidioidal infections, CF antibodies are detected somewhat later and for longer periods than TP antibodies. CF antibodies can be detected in other body fluids and their detection in the cerebrospinal fluid is an especially important aid to the diagnosis of coccidioidal meningitis.

Another difference between CF and TP antibodies is that CF results are expressed as titers, such as 1:4 or 1:64, indicating the greatest dilution of serum at which complement consumption is still detected. In general, higher CF titers reflect more extensive coccidioidal infection, and rising CF antibody concentrations are associated with worsening disease. Thus, serial determinations of CF antibody concentrations are of prognostic as well as diagnostic value.

Immunodiffusion Tests (IDTP, IDCF)

Antibodies that were detected by the original TP or CF tests can be detected by an alternative procedure known as the immunodiffusion (ID) tests (IDTP and IDCF, respectively). Although the conduct of the IDTP and IDCF tests is quite similar, each uses a different antigen to measure different types of antibodies.

As with the original tests, the IDTP is reported by some laboratories as the “IgM test” and the IDCF as the “IgG test” result. Both tests have been found to be at least as sensitive as their original counterparts. Moreover, immunodiffusion tests are amenable to being manufactured and distributed as commercially prepared kits, thus allowing the tests to be performed in labs not fully dedicated to a mycology specialty.

Enzyme-linked Immunoassays (EIA)

An EIA test for coccidioidal antibodies is available commercially. The test kit allows for the specific detection for IgM or IgG antibodies. However, these results are not interchangeable with IgM or IgG test results. Positive EIA results are highly sensitive for coccidioidal infection. However, false-positive results have been noted with the IgM EIA test. How frequently this occurs is not a settled issue (6-8).

Latex Tests

Latex tests for coccidioidal antibodies are also commercially available. They are attractive to clinical laboratories because of their ease of use and rapidity of obtaining a result. However, there are significant numbers of false-positive reactions, and therefore a positive latex test is not as reliable as any of the other tests described in this section.

Cultures for Coccidioides spp. 

Isolating Coccidioides spp. from sputum or another clinical specimen is definitive evidence of a coccidioidal infection. Despite this, early infections are usually not diagnosed by culture. The reasons why cultures are not routinely obtained in the ambulatory care setting are related to several factors.

First, fungal cultures are an unusual request in the ambulatory care setting. Although it would be valuable if this were to change, requesting fungal cultures on a sputum specimen currently may be disruptive to workflow. Another consideration is that patients with coccidioidal pneumonia may not be able to produce a specimen for culture. While this problem can usually be circumvented, it takes extra steps. Finally, there is a potential risk to laboratory personnel of isolating Coccidioides spp.

Laboratories handling fungal cultures should be thoroughly versed in safe- handling of such specimens and culture medium, and small outpatient laboratories may not be so equipped or trained. None of these considerations are absolute barriers to obtaining culture confirmation. Since negative serologies do not exclude the diagnosis of coccidioidomycosis, cultures may be the only way to obtain a timely diagnosis in some patients. As a general rule, the more serious the illness, the more likely fungal cultures should be considered as an essential part of the diagnostic evaluation.

Handling of Specimens

Sputum or other clinical specimens should be collected in a sterile container. This may be done in the clinic at no risk to personnel, since the infection is not transmitted from the primary specimen. Patients with scant sputum can be asked to take a specimen cup home with them and collect a specimen early in the morning (when sputum is usually more readily retrievable) and then return the cup.

Such specimens can be stored refrigerated until transfer to the medical facility. For more serious problems, other respiratory secretions (bronchoscopic aspirates) and tissue specimens (skin or bone biopsies) can be submitted for culture.

Laboratory Evaluation

Direct examination of secretions can be performed immediately or after the addition of potassium hydroxide. Although culture results are more sensitive than direct examination, identification of spherules in this way is diagnostic and very rapid. Coccidioides spp. cannot be detected by Gram staining. However, spherules can be seen with cytology stains such as are performed on bronchoscopy specimens, by hematoxylin and eosin stains of tissue sections, and with other specialized stains.

Coccidioides spp. are not particularly fastidious and grow well on most mycologic and bacteriologic media. Furthermore, growth usually develops within four to seven days of incubation. Some clinical laboratories within the coccidioidal endemic region have used these characteristics to advantage by holding all routine bacteriologic sputum cultures for a week before discarding the plates, since some patients who are thought to have bacterial pneumonia will actually yield Coccidioides spp.

When growth occurs, it is typically as a white (nonpigmented) mold. However, there are many exceptions to this general appearance, and the morphologic appearance is not reliable in determining if the fungus is or is not Coccidioides spp.

Once growth is evident on culture medium, care should be taken not to open the culture container except in an appropriate biocontainment cabinet. Cultures at this stage are infectious and can cause disease in persons exposed to them unless the cultures are properly handled. Since the morphologic appearance of Coccidioides spp. is not sufficient to determine the species, additional laboratory testing must be carried out for specific identification.

The most common way for microbiologists to perform additional testing is to detect a specific DNA sequence using a commercially available DNA probe. Smaller laboratories often refer the culture to a reference laboratory where species identification is completed.

As of December 2012, Coccidioides spp. are no longer designated select agents by the Centers for Disease Control and Prevention (CDC).

Skin Testing

Dermal hypersensitivity to coccidioidal antigens is highly specific for past coccidioidal infection, and if used in patients when they are healthy, it can index patients as to whether they are at risk of future illness due to Valley Fever.

For example, persons who demonstrate a reactive skin test are very likely to be immune for life and have little chance of future coccidioidal problems. On the other hand, for those who do not react, Valley Fever remains a possible etiology in a future illness. However, because skin test results remain positive after infection in most persons for life, it may not relate to the current illness. In addition, some of the most serious infections may be associated with selective anergy, and the skin test may not demonstrate reactivity.

Therefore, as useful as skin test results are for indexing risk in patients while healthy, important limitations exist when used as a screening procedure for recent or current infection. If Valley Fever is diagnosed by other means, skin testing may have prognostic significance, as patients with progressive infections often fail to develop dermal reactivity to coccidioidal antigens. Since the 1990s, there was no coccidioidal skin test commercially available. However, a company (Nielsen BioSciences, San Diego, CA) has redeveloped a spherule-based skin test antigen (SPHERUSOL®) and has received approval from the FDA to market it.

Results of a skin test are measured at 48 hours after the antigen is injected intradermally. Induration of greater than 5 mm is considered reactive. Erythema at the injection site is not of diagnostic value. Coccidioidal skin testing does not influence coccidioidal serology results.

Check for Risk Factors

The First Step Postdiagnosis

Once a diagnosis of coccidioidal infection is established, the next step is to review any possible risk factors that might make the patient particularly susceptible to complications. This is usually accomplished during a complete history and physical examination.

Immunosuppression

By far the most clearly demonstrable risk of complications from a coccidioidal infection is the coexistence of major immunosuppressive conditions that adversely affect cellular immunity. These would include immunosuppression to prevent rejection of organ transplants, AIDS in HIV-infected persons, and anti–tumor necrosis factor therapy for rheumatologic conditions. For example, the risk of infections extending beyond the lungs in renal transplant recipients can be as high as 75%. This risk is much greater than the risk of a similar complication in the general population.

Immunosuppressive conditions that affect humoral immunity appear to have relatively little risk for complications of coccidioidal infection. Similarly, splenectomy, hypocomplementemia, or neutrophil dysfunction syndromes are not major risk factors for this disease.

Diabetes Mellitus

Patients with diabetes appear to have an increased risk of pulmonary complications (9). While many of such patients resolve their initial infection without residual problems, a disproportionate number seem to develop symptoms related to pulmonary cavities and chronic pneumonia. There is little or no evidence that this group of patients is at increased risk for developing extrapulmonary infections.

Pregnancy

Women who contract Valley Fever during pregnancy are at particular risk of serious infection. Those at highest risk for serious infection are women diagnosed during the third trimester or immediately postpartum. Such infections may be life-threatening and should be regarded as complicated management problems.

Other Risk Factors

There are additional factors that should be considered relevant to the risk of complications from coccidioidal infection. Complications are more frequent in men than in women and in adults than in children. Life-threatening infections are more common in the elderly. Recent evidence suggests this is related in part to accumulated comorbidities in aging persons rather than age itself (10).

In addition, there appears to be an increased risk of disseminated infection among African Americans, Filipinos, and perhaps other racial groups. Racial predilection for complications is somewhat conjectural since the exact definitions of racial groups are in dispute and carefully controlled epidemiologic studies are not available. Even if racial differences exist (as most authorities believe), the increase in risk may be only four-fold above that of the population as a whole.

Check for Progressive Pulmonary Syndromes or Disseminated Disease

Assessing Complications

Even in the absence of the risk factors previously discussed, it is important to assess patients with coccidioidal infections for complications because they can also occur in patients without apparent reason.

Complications from initial coccidioidal infections are divided into those that  occur in the chest and those that involve parts of the body outside of the lungs (extrapulmonary dissemination). These two types of complications usually do not overlap. Most complications produce localized symptoms and signs of chronic or subacute inflammation. As a result, a careful review of symptoms and physical examination are usually a sufficiently sensitive initial screen.

Most complications manifest within the first year or two after the initial infection. If a new complaint develops in association with a recent coccidioidal infection, its possible relationship to the infection should be considered. For example, in general practice, low back pain is a common symptom, and mild discomfort is often managed symptomatically before extensive diagnostic studies are undertaken.

However, if this symptom were to occur in a patient within weeks or months of developing coccidioidal pneumonia, it may be useful to recommend a radionuclide scan to determine if the new symptom is due to infection in the lumbar vertebrae. This is done to detect complications early, before serious tissue destruction occurs. Similarly, persistent or progressive headaches, skin lesions, or joint effusions in the context of a recently diagnosed coccidioidal pneumonia might warrant more detailed investigation with lumbar puncture, biopsy, or aspiration, respectively.

Persistent or Slowly Resolving Pneumonia

Most pulmonary infections are subacute in nature. Without treatment, symptoms usually improve within the first month but may not completely resolve for several months. In some patients, the course of illness is even more protracted. There is no consensus regarding how protracted illness must be before it is considered as slowly resolving. However, in studies of new therapies for coccidioidomycosis, entry criteria often specify that pulmonary disease must have been present for at least three months. In clinical practice, shorter periods of illness may be more reasonable.

Pulmonary Cavitation

Cavities form in approximately 5% of patients with coccidioidal pneumonia. Half of these cavities will disappear within the first two years. Many cavities cause no symptoms. Others cause discomfort, cough, hemoptysis, and occasionally constitutional symptoms of fatigue, night sweats, and weight loss. Occasionally, a coccidioidal cavity will rupture into the pleural space. This usually has an abrupt onset and consequently leads to prompt evaluation. Given the peripheral nature of many coccidioidal cavities, this event is surprisingly uncommon.

Chronic Fibrocavitary Pneumonia

A few patients experience repeated development of pneumonia over a period of many years. Sometimes, this includes different lobes of the lung.

Diffuse Fulminant Pneumonia

In some patients, coccidioidal pneumonia is very severe, causing hypoxia and requiring respiratory support to prevent respiratory collapse. This is obviously a major complication and is handled very differently than most infections.

Extrapulmonary Dissemination

When infection spreads beyond the lungs, it usually does so within the  first several months after the initial infection and nearly always within the first two years. In this way, coccidioidal infections differ from tuberculosis, which commonly returns decades after the initial infection. An important exception to this rule is in the intervening development of major degrees of immunosuppression of the nature discussed previously. The most common sites of dissemination are skin, joints, bones, and the meninges. However, virtually any part of the body can be affected.

Initiate Management

Strategies for Uncomplicated Early Infections

Once a diagnosis of coccidioidal infection is established and a thorough evaluation for enhanced risk and evidence of complications has been accomplished, a rational management strategy can be formulated.

Patients who do not have risk factors, symptoms, or physical findings suggestive of progressive infection can be classified as having early uncomplicated infections. In general, a majority of patients will fall into this category and might be safely managed by primary care practitioners. The remainder may benefit from consultation with a specialist in infectious diseases, pulmonary diseases, neurology, or other disciplines to aid in developing a treatment plan. Management of complicated coccidioidal infections is beyond the scope of this monograph, but comprehensive treatment guidelines are available.

General guidelines for managing patients with uncomplicated infections are outlined in Figure 4.

Figure 4. Managing uncomplicated coccidioidomycosis.

Health Education and Recommendations to the Patient and Family

Very commonly, establishing a diagnosis will be of great help to the patient because it clearly identifies the nature of the illness and allows the health care provider the opportunity to explain what may happen in the future. A general review of how patients contract Valley Fever, the typical symptoms, the need for therapy, or the lack of the need for therapy, may be helpful to put the patient’s experience in a more general and knowledgeable context.

Patient information leaflets have been prepared to facilitate this process and are available from the Valley Fever Center for Excellence.

Explaining that the illness usually improves slowly over a period of weeks to even months will be useful in allowing patients to align their expectations with the natural history of the illness. The patient can be advised that he or she cannot transmit the infection to others and therefore poses no risk to others.

Although the prognosis is generally favorable for most patients, it is important to explain to patients some of the infrequent but possible complications, both pulmonary and extrapulmonary. Worsening respiratory symptoms should prompt reevaluation, and new focal symptoms outside of the chest should be noted and, if they persist, be brought to the attention of the treating clinician. Explaining the need for follow-up to the patient even as the infection resolves without therapy should improve adherence to follow-up care.

Frequency of Follow-Up Health Care Visits

Continued follow-up is, in fact, at the core of the management of uncomplicated coccidioidal infections. This is needed to confirm that the illness remains uncomplicated and that more specific interventions are not necessary.

In addition, residual pulmonary abnormalities may remain, which should be documented for future reference so that they are not unnecessarily reevaluated as a new problem years later. In rare instances, coccidioidal infections and lung neoplasms have coexisted, and this possibility should be considered during the follow-up period.

The interval between medical visits varies according to the severity of the symptoms and the course of infection up to the point of diagnosis. If symptoms are still worsening, follow-up visits or telephone contact might be appropriate within days to a week later, since continued worsening may prompt reevaluation and the initiation of antifungal therapy.

On the other hand, if there is clear evidence of improvement, then a return visit might be appropriate in two to four weeks. After the first two or three visits, the intervals between visits typically range from one to several months. By two years, an uncomplicated coccidioidal infection can be considered resolved.

Monitoring the Course of Infection

Several clinical and laboratory findings are helpful to assess the course of infection. Generally, systemic signs of fever, night sweats, and weight loss are the first to abate as a coccidioidal infection improves. The respiratory symptoms of chest pain, cough, and sputum production may be more protracted.

Not infrequently, fatigue and an inability to resume normal activities are some of the last symptoms to resolve. Since this is commonly a chronic process, patients may fail to see changes in these symptoms from day to day, and only when asked to compare their current state with one week or one month earlier do they become cognizant of improvements. Often, having the patient keep a journal with entries every other week is a helpful tool to document progress.

Laboratory tests can also be helpful in providing objective evidence of improvement. Erythrocyte sedimentation rate, often elevated with early coccidioidal infections, is an inexpensive measure of systemic inflammation and can be used to monitor progress. Typically, this would not be measured any more often than on a weekly basis. In addition, the CF or IDCF antibody concentration is expected to decrease as a coccidioidal infection resolves, and it is important to demonstrate this response. If these results do not normalize as expected, concern should be raised that complications may be developing and that further diagnostic studies may be in order. Repeated serologic testing should seldom be any more frequent than every two weeks and usually ranges from one to several months between tests.

A suggested plan for follow-up timing for review of systems (ROS), physical examination, coccidioidal CF tests, and chest radiographs is shown in Table 7.

Table 7. Suggested Plan for Follow-up Visits.

Chest radiographs should be repeated to demonstrate either resolution of all pulmonary abnormalities or to document what residual abnormalities persist. Early in the course of infection, the interval may be as frequent as several days until symptoms or radiographic findings demonstrate that abnormalities are stable or improving. Subsequent chest radiographs should be obtained either every several weeks or every several months. Often, two views of the chest are sufficient to monitor progress, and the increased sensitivity of CT scans is not usually needed as the patient improves.

Antifungal Therapy

For early uncomplicated coccidioidal infections, most patients can be managed without antifungal therapy. There are currently five commercially available oral antifungal drugs with activity for treating coccidioidal infections: ketoconazole, fluconazole, itraconazole, voriconazole, and posaconazole. Published reports have demonstrated activity of all of these agents in treatment of complicated coccidioidal infections, but there are no randomized trials demonstrating that any of these drugs shorten the course of early uncomplicated infections or prevent later complications. Two recent observational studies also provide no evidence for a beneficial effect in the pharmacologic treatment of early coccidioidal pneumonia (11,12).

Given this uncertainty, the decision whether to initiate antifungal drug therapy for uncomplicated coccidioidal pneumonia is highly individualized. This issue is addressed further in the Infectious Diseases Society of America (IDSA) Practice Guidelines (13). Treatment with fluconazole or itraconazole for such patients typically involves doses ranging from 200 to 400 mg per day, with treatment durations ranging from several to many months.

Treatment of complicated infections is beyond the scope of this monograph but is also addressed in the IDSA Practice Guidelines. The length of treatment for such patients ranges from one year to the entire course of the patient’s lifetime, depending upon the location of the infection and underlying risk factors.

The cost of therapy is substantial. Drug costs alone range from $2,000 to $20,000 per year, depending upon the specific drug and the daily dose prescribed.

Physical Therapy Reconditioning As an Approach to Persistent Fatigue

Not infrequently, patients who resolve all evidence of active infection continue to be disabled because of profound fatigue. For example, in a study from the University of Arizona that compared the impact of Valley Fever to mononucleosis, twice as many students with Valley Fever dropped out for a semester (14). It is very possible that this persistent symptom is a consequence of patients becoming deconditioned as a consequence of the fatigue that Valley Fever first produces.

If that is true, then referral to a physical therapist to assist the patient with a reconditioning program might be very helpful to hasten recovery. The Valley Fever Center for Excellence has initiated this practice, and the preliminary results have been encouraging.

Conclusion

Valley Fever represents a substantial public health problem, the true burden of which likely remains under-recognized. The clinical presentation of this disease is often non-specific, and increased awareness among clinicians, particularly those involved in primary care, about the disease is essential in order to ensure that patients with Valley Fever receive a timely and accurate diagnosis. Clinicians should maintain a high clinical suspicion for Valley Fever in patients who live in the endemic region or who have traveled to these areas. Although only a small proportion of patients with Valley Fever develop pulmonary complications or extrapulmonary disease, it is important to identify these complications as early as possible. For the other patients, most coccidioidal infections are uncomplicated. The five steps—Consider the diagnosis, Order the right tests, Check for risk factors, Check for complications, and Initiate management (COCCI)—are a simple way for generalists to identify those with complications and to manage uncomplicated infections without specialty referral.

References

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Additional Selected References

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Reference as: Galgiani JN. Valley fever (coccidioidomycosis): turtorial for primary care physicians. Southwest J Pulm Crit Care. 2015;10(5):265-88. doi: http://dx.doi.org/10.13175/swjpcc073-15 PDF PDF in booklet form