Spirometry Use in Patients Prescribed Albuterol

Kevin Park, M.D.

Che' S. Ornelas, M.D.

Richard A. Robbins, M.D.

Phoenix VA Medical Center, Banner Good Samaritan VA Medical Center and the Phoenix Pulmonary and Critical Care Medicine and Research Foundation, Phoenix, AZ

Address correspondence to:     Richard A. Robbins, M.D.

                                             502 E. Vermont Drive

                                             Gilbert, AZ 85295

                                             E-mail: rickrobbins@cox.net

Conflict of Interest Statement: None of the authors have conflicts of interest pertinent to the subject matter of this manuscript. 

Abstract

Background:  Previous studies have shown that spirometry is obtained in only about a third of patients with chronic obstructive pulmonary disease (COPD) in primary care practice. This study evaluated spirometry use in persons prescribed an albuterol inhaler in the primary care clinics at a Veterans Administration (VA) hospital.

Methods: One hundred ninety-seven patients prescribed albuterol were reviewed for age, education level of the primary care practioners, other respiratory medications and diagnosis.

Results: The average age was 63.2 years (SD, 11.5), and 93% of patients were male. Obtaining spirometry was not age or sex-dependent but became more frequent with the use of tiotropium (72.2%), long-acting beta agonists (71.8%), ipratropium (69.4%)  or inhaled corticosteroids (63.5%) compared to albuterol alone (39.4%, p=0.0007). Eighty of the patients had a diagnosis of COPD (40.6%), 40 a diagnosis of asthma (20.3%), 23 other respiratory diagnoses (11.7%) but 54 (27.4%) had no respiratory diagnosis. Patients diagnosed with COPD were more likely to have spirometry performed (71.2%) than patients diagnosed with asthma (35%), other respiratory diagnosis (34.7%) or no respiratory diagnosis (40.7%) (p=0.00068).

Conclusions: The above data demonstrate that spirometry is more frequently used in patients with COPD than previously reported and increases when additional medications are added to albuterol.

Introduction

Spirometry is recommended for the diagnosis of most adult respiratory disease including chronic obstructive pulmonary disease (COPD) and asthma (1-5). However, previous publications have revealed that in patients with COPD spirometry is performed in only about a third of the patients (6-10). Based on this data, we initiated a quality improvement project to examine compliance with spirometry guidelines in primary care.

Most previous investigations have examined patients’ diagnosis of COPD or asthma and examined the percentage of patients who had spirometry. However, the diagnosis of COPD or asthma is frequently incorrect (11-13). Furthermore, these projects may likely both under- and over-diagnose COPD in patients with no symptoms (14). Since albuterol is recommended as initial treatment for both diseases (1-4), we examined recent prescriptions for albuterol at a single VA medical center. Our rationale was that this should eliminate asymptomatic patients or patients with very mild disease. We found that in patients prescribed albuterol who also had a diagnosis of COPD that spirometry was performed over double (72%) of previous reports.

Methods

This project was approved by the institutional review board of the Carl T. Hayden VA Hospital. Using VA records we identified 200 patients seen in primary care who were prescribed an albuterol inhaler and had a primary care visit between November 1-5, 2010 or November 8-12, 2010. The electronic records were reviewed for each patient. Demographic data (age, sex); education level of provider (MD or DO, nurse practioners); diagnosis (COPD, asthma, other respiratory diagnosis or no diagnosis); other respiratory medications, and the presence of spirometry were recorded. When spirometry was available for COPD patients, spirometric values of FEV1/FVC% or FEV1% predicted were recorded and used to classify COPD severity based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (1,15).

Statistical Analysis

Comparisons between the groups with and without spirometry were made with χ2 tests for categoric variables and t tests for continuous variables. The association between having spirometry performed and patient characteristics was evaluated in unadjusted models.

Results

Chart review

Two hundred charts were examined, but 3 patients were excluded, one because they had not been prescribed albuterol and two because of incomplete data. The remaining 197 patients were evaluated.

Demographics

Age was 63+11 years and 7% of the patients were female. Age and sex were not significantly different between those who had spirometry and those who did not (data not shown, p>0.05 both comparisons).

Education Level of Provider

There were 16 MD or DO physician primary care providers and 8 nurse practioners. The physicians saw 136 patients and the nurse practioners 61. Spirometry was present on 73 of the patients seen by physicians (53.7%) and 29 of the patients seen by nurse practioners (47.5%, p=0.45).

Other Respiratory Medications

Numbers of patients with other respiratory medications are shown in Table 1. Many patients were on multiple medications. Patients on albuterol alone were significantly less likely to have spirometry than those on other medications (p=0.0007). Only two patients were receiving theophylline and one oral prednisone.

Table 1. Spirometry and other respiratory medications prescribed

LABA=Long-acting beta agonist

ICS=Inhaled corticosteroid

*p=0.0007 compared to other medications

Diagnosis

COPD was diagnosed in 80 patients (40.6%), asthma in 40 patients (20.3%), other respiratory diagnosis in 23 patients (11.7%) but no respiratory diagnosis was recorded in 54 patients (27.4%). Other respiratory diagnosis included 10 patients with tobacco dependence, 3 with dyspnea, 2 with lung carcinoma, and 2 with obstructive sleep apnea and one each with allergies, cannabis dependence, sinusitis, coin lesion, pulmonary embolus and respiratory disorder not otherwise specified. Patients with COPD were significantly more likely to have spirometry performed than other diagnosis (Table 2).

Table 2. Spirometry and respiratory diagnosis

*p=0.00068 compared to other diagnosis

Of the 57 patients with COPD and spirometry, 5 had very severe disease (FEV1 <30% predicted), 16 had severe disease (30% < FEV1< 50% predicted), 34 had moderate disease (50% < FEV1 < 80% predicted) and 2 had mild disease (FEV1>80% predicted) by GOLD criteria. Six of the 18 COPD patients without spirometry were receiving albuterol alone compared to 11 of the 57 of the COPD patients with spirometry (p=0.5519).

Discussion

The objective of this study was to examine spirometry use in primary care in patients with prescribed albuterol. Overall, the presence of spirometry in patients was low, with only 51.8% of patients having spirometry performed during the analysis period. Patients diagnosed with COPD or who had additional respiratory medications prescribed in addition to albuterol were more likely to undergo spirometry. In the present study, 71.8% of patients with COPD received spirometry.  This is more than twice the percentage of previous reports where only about a third of COPD patients had spirometry performed (6-10).

Spirometry is performed in some general medicine clinics, but in our hospital spirometry is performed in the pulmonary function laboratories or in the pulmonary clinic, a situation that may differ from many health-care systems. However, a previous report from a VA hospital reported only about a third of newly diagnosed COPD patients received spirometry (7). Our study differs in several aspects which might explain at least part of the variance. First, rather than looking at a diagnosis of COPD, we examined patients who were prescribed albuterol. This includes patients with asthma and other respiratory diagnosis. Second, we included patients with long-standing COPD rather COPD recently diagnosed. Previous reports suggest that as the number of visits increases that the likelihood of spirometry also increases (10). Third, many patients are “co-managed”, that is they received health care elsewhere in addition to the VA. It is entirely possible that they may have had spirometry performed elsewhere which is not available in our medical record. However, in contrast to previous studies, chart reviews were performed on each patient. If the patient had a previous spirometry recorded in the chart from another institution this should have been noted in our study. Fourth, the VA pharmacy placed restrictions on primary care physicians prescribing long-acting bronchodilators, especially tiotropium. These patients were usually referred to our pulmonary clinic where spirometry was usually required prior to referral.

Several factors have been previously identified that are related to lower rates of spirometry. Age had been reported as the factor with the most pronounced impact on decreasing the likelihood of undergoing spirometry in a VA population (6). However, we found no influence of age on the likelihood of spirometry performance. COPD diagnosis has also been reported to have a decreased likelihood of spirometry performance (8), but in contrast, we found that COPD actually increased the likelihood of spirometry performance. The use of theophylline has also been associated with decreased levels of spirometry performance. However, only about 1% of our patients were prescribed theophylline.

There are several limitations to our study. First, it is a single site study. It is possible that our primary care physicians are more likely to order spirometry because of increased awareness or restrictions in prescribing long-acting bronchodilators or referral to a pulmonary clinic. Previous reports from the VA have demonstrated that there is a large geographic variation in the use of spirometry to diagnose COPD (8). The location of the present study was in Veterans Integrated Service Network 18 (Arizona, New Mexico and West Texas) where spirometry use (36.9%) approximated the National mean (36.7%). It is unclear whether the results from the present study can be generalized to the VA as a whole or non-VA institutions is unclear. Second, we examined patients prescribed an albuterol inhaler rather than those with a diagnosis of COPD or asthma. This likely eliminates many patients with mild or no symptoms which differs from previous studies. The US Preventive Services Task Forces has recommended against screening asymptomatic patients with spirometry (16).

The patients with no diagnosis given albuterol were a heterogenous group and the indications for the use of albuterol were often absent or unclear. Although albuterol can be empirically prescribed for asthma, cough or COPD, the indications for albuterol were absent in the majority of charts.

This study suggests that in contrast to previous reports, much of the current COPD diagnosis and management is based on spirometric evidence of airway obstruction in addition to symptoms. Although the role of spirometry in routine clinical practice remains unclear, primary care providers at our VA hospital appear to frequently use spirometry in patients with COPD.

References

1. Global Strategy for the Diagnosis, Management and prevention of Chronic Obstructive Pulmonary Disease 2011. Global Initiative for Chronic Obstructive Lung Disease (GOLD) www.goldcopd.com (accessed 1/26/11).
2. Qaseem A, Wilt TJ, Weinberger SE, Hanania NA, Criner G, van der Molen T, Marciniuk DD, Denberg T, Schünemann H, Wedzicha W, MacDonald R, Shekelle P; American College of Physicians; American College of Chest Physicians; American Thoracic Society; European Respiratory Society. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med 2011;155:179-91.
3. National Committee for Quality Assurance. HEDIS 2006: health plan employer data & information set, vol 2; technical specifications. Washington, DC: National Committee for Quality Assurance, 2005; 350
4. Expert panel report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. NHLBI. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (accessed 12/10/11).
5. Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, Busse WW, Casale TB, Chanez P, Enright PL, Gibson PG, de Jongste JC, Kerstjens HA, Lazarus SC, Levy ML, O'Byrne PM, Partridge MR, Pavord ID, Sears MR, Sterk PJ, Stoloff SW, Sullivan SD, Szefler SJ, Thomas MD, Wenzel SE; American Thoracic Society/European Respiratory Society Task Force on Asthma Control and Exacerbations. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical  asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59-99.
6. Han MK, Kim MG, Mardon R, et al. Spirometry utilization for COPD: How do we measure up? Chest 2007;132:403-09.
7. Lee TA, Bartle B, Weiss KB. Spirometry use in clinical practice following diagnosis of COPD. Chest 2006;129(6):1509-15.
8. Joo MJ, Lee TA, Weiss KB. Geographic variation of spirometry use in newly diagnosed COPD. Chest 2008;134:38-45.
9. Arne M, Lisspers K, Ställberg B, Boman G, Hedenström H, Janson C, Emtner M. How often is diagnosis of COPD confirmed with spirometry? Respir Med. 2010;104:550-6.
10. Anthonisen NR, Woodlrage K, Manfreda J. Use of spirometry and respiratory drugs in Manitobans over 35 years of age with obstructive lung diseases. Can Respir J 2005;12:69-74.
11. Marklund B, Tunsäter A, Bengtsson C. How often is the diagnosis bronchial asthma correct? Fam Pract 1999;16:112-6.
12. Tinkelman DG, Price DB, Nordyke RJ, Halbert RJ. Misdiagnosis of COPD and asthma in primary care patients 40 years of age and over. J Asthma. 2006;43:75-80.
13. Zwar NA, Marks GB, Hermiz O, Middleton S, Comino EJ, Hasan I, Vagholkar S, Wilson SF. Predictors of accuracy of diagnosis of chronic obstructive pulmonary disease in general practice. Med J Aust 2011;195:168-71.
14. Enright P. Use and abuse of office spirometry. Primary Care Respiratory Journal 2008;17: 238-242.
15. Knudson RJ, Lebowitz MD, Holberg CJ, Burrows B. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis 1983;127:725-34.
16. US Preventive Services Task Force. Screening for Chronic Obstructive Pulmonary Disease Using Spirometry. Available at  http://www.uspreventiveservicestaskforce.org/uspstf08/copd/copdrs.htm (accessed 12/12/11).

Reference as: Park K, Ornelas CS, Robbins RA. Spirometry use in patients prescribed albuterol. Southwest J Pulm Crit Care 2011;4:25-9. (Click here for a PDF version of the manuscript)

A 39 Year Old Female with Progressive Dyspnea, Dry Cough and Hypoxia: A Case Report

Sabeen Yaqub, MD 

Michelle S. Harkins, MD

Division of Pulmonary, Critical Care and Sleep Medicine

Department of Internal Medicine.

University on New Mexico

Albuquerque, NM 87131

Emails: sabeenyaqub@gmail.com

             MHarkins@salud.unm.edu

None of the authors of the above manuscript has declared any conflict of interest, which may arise from being named as an author on the manuscript.

Reference as: Yaqub S, Harkins MS. A 39 year old female with progressive dyspnea, dry cough and hypoxia: a case report. Southwest J Pulm Crit Care 2011;3:134-40. (Click here for a PDF version of the manuscript)

 Case Presentation

A previously healthy 39 year old female presented with progressive shortness of breath on exertion, dry cough, fatigue, fevers and hypoxia for the last four months. Her symptoms worsened despite being on several courses of antibiotics. Her past medical history is significant for hypertension and diabetes and medications include metoprolol and fosinopril. There is no previous history of cigarette smoking, drugs or alcohol abuse. She denied any weight loss. She was evaluated by a pulmonologist at an outside facility before being transported to our facility. Workup included chest x-ray and CT scan which showed patchy areas of consolidation. A bronchoscopy with bronchial alveolar lavage (BAL) was also performed but she became profoundly hypoxic and was transferred to the ICU intubated.

Physical Exam

An obese female who was intubated and sedated on pressure targeted ventilation with delta P 28, rate 15, FiO2 60% peep 8. Her vitals revealed a T_max of 38.6 C and blood pressure of 146/85. There were coarse breath sounds bilaterally and mild diffuse crackles in all lung fields. No clubbing or cyanosis was noted. The rest of the exam was unremarkable with a normal abdominal, cardiac and skin exam.  There was no adenopathy.

Labs

Complete blood count, electrolytes and liver function tests were normal.  HIV testing was negative.

Radiological findings

Chest x-ray demonstrated perihilar and bibasilar opacities.

CT scan is shown below in Figure 1.

Figure 1: CT Scan - Diffuse and geographic ground glass opacities accompanied by interlobular septal thickening consistent with the classic “crazy paving” with geographic distribution.

Bronchoscopy

Bronchoscopy with bronchoalveolar lavage (BAL) was performed which revealed an opaque appearing fluid with particulate matter. An open lung biopsy was performed to confirm the suspected diagnosis.

Pathology

Open Lung Biopsy revealed normal alveolar architecture with eosinophilic staining debris within the alveolar spaces that was Periodic Acid Schiff (PAS) + (Figure 2).

Figure 2: Open Lung Biopsy: Numerous alveolar spaces filled with abundant eosinophilic material (A) which is PAS positive (B) and occasional dense globular clumps with intra-alveolar macrophages. The alveolar septae are delicate without evidence of fibrosis.

Diagnosis:  Pulmonary Alveolar Proteinosis (PAP)

Hospital Course 

She underwent a partial whole lung lavage of the right lung first and remained intubated post procedure.  She underwent a repeat lavage of the right lung four days later and then a whole lung lavage on the left one week later due to bilateral infiltrates and difficulty weaning from the ventilator. Each lavage consisted of 12 liters of warmed saline and there was progressive clearing of the cloudy material obtained by the end of the lavage.  BAL cultures were obtained which were positive for Staphlococcus aureus and Klebsiella but were negative for Nocardia, Pneumocystis, and acid fast bacilli. She was treated with antibiotics for 7 days for the bacterial infection.  She was then successfully extubated.

Discussion

PAP also known as pulmonary alveolar phospholipoproteinosis is a diffuse lung disease characterized by accumulation of amorphous PAS+ lipoproteinaceous material in the distal airspaces with little or no inflammation and preservation of the underlying lung architecture.^1-3

Three forms of PAP are recognized; congenital, secondary and acquired. Congenital form is present in neonates and results from mutations in genes for surfactants or GM-CSF receptors. The acquired form is the most common and GM-CSF antibodies contribute to macrophage dysfunction and impaired processing of surfactant. The secondary form is associated with high level dust exposure (silica, aluminium, titanium), hematologic malignancy and after allogenic bone marrow transplant for myeloid malignancy and infection (Nocardia, viral, Pneumocystis). Macrophages are overwhelmed by accumulation of surfactant rich material and they lose the ability to phagocytize.

Clinical signs and symptoms include dyspnea on exertion, cough, fatigue, weight loss and low grade fevers.  Clubbing, cyanosis and crackles on physical exam may be present. Patients with PAP have an increased risk of opportunistic infection with Nocardia, Mycobacteria, fungi and Pneumocystis due to impaired macrophage and neutrophil function. Laboratory abnormalities include polycythemia, hypergammaglobulinemia, and increased LDL. On Chest x-ray bilateral symmetrical alveolar opacities are located centrally in the mid and lower lung zones in a ‘bat wing’ distribution. CT scan reveals heterogenous distribution of ground glass opacification and septal thickening.

The diagnostic work-up should include a history and physical consistent with PAP, a CT scan, fiberoptic bronchoscopy to obtain lavage fluid and transbronchial biopsies and serum assay for Anti-GM-CSF antibodies.  To exclude the presence of concurrent infections special stains and cultures for opportunistic infection should be obtained. In one of the largest cohort studies of 248 PAP patients, diagnosis was made by High Resolution CT (HRCT) scan and BAL in 59%; HRCT, BAL and transbronchial biopsy in 34% and VATS biopsy in 7%.⁴ Characteristic findings on BAL are an opaque or milky appearance due to abundant lipoproteinaceous material, alveolar macrophages that are engorged with PAS positive material, increased SP-A levels and large acellular eosinophilic bodies. On histological specimens, the normal alveolar architecture is preserved although the alveolar septa may be thickened due to type-2 cell hyperplasia. There is little or no inflammatory cell infiltrate. The terminal bronchioles and alveoli are filled with PAS positive lipoproteinaceous material.

The treatment options vary with the severity of disease. In the cohort study, asymptomatic patients were the most likely to have a stable course and only 8% worsened during follow up. ⁴ Among symptomatic patients the proportion of stable, improved and worsening disease was 45%, 30%, and 25% respectively. Patients with longer duration are likely to have progressive disease.

Asymptomatic patients can be observed with periodic reassessment of symptoms, pulmonary function testing (PFTs) and chest x-rays (CXRs). In patients with mild symptoms (mild hypoxia on exertion, normoxia on rest) supplemental oxygen is appropriate. Patients with moderate to severe disease may elect for whole lung lavage or a trial of experimental treatment with GM-CSF or plasmapheresis. Whole lung lavage under general anesthesia via a double lumen endotracheal tube is recommended for patients who have moderate to severe disease.^5-7 Indications for lung lavage include resting PaO2 <65, A-a gradient >40, shunt fraction>10-12% and severe hypoxia or dyspnea on rest and exertion. Clinical course is variable. Thirty-forty percent of patients require one lavage while others require lung lavage at intervals of 6-12 months.

Experimental therapy with GM-CSF has been used. ^8-13 In an open trial of 25 patients, GM-CSF was given subcutaneously and 48% experienced symptomatic and radiological improvement. However the proportion of responders to whole lung lavage appears to be the largest.^11-12 Given the experimental nature of GM-CSF therapy, lung lavage as primary therapy is recommended. Lung transplant is reserved for patients who deteriorate despite whole lung lavage but recurrence in allograft has been reported.¹⁴ Treatment with rituximab and plasmapheresis have had mixed results.^15-16 Though the most recent open label trial of rituximab given in 10 PAP patients demonstrated that it is well tolerated and improved oxygenation parameters up to six months after therapy and may have decreased the need for whole lung lavage.   The exact mechanism of benefit is unclear but is likely related to clearing of the autoantibodies present in the lung.¹⁷ There is no role for glucocorticoids as therapy for PAP.  

Follow up in our patient

The patient was followed in clinic after discharge. She continued to complain of an increased cough productive of clear mucus. She denied any changes in activity level or shortness of breath. PFTs were slightly worse than before. CT chest was concerning for increased bilateral densities.  She had a GM-CSF antibody titer of 1:6400 which confirms acquired PAP (a 1:400 titer is considered abnormal).

She was given a 3 month trial of inhaled GM-CSF and seen in clinic after 3 months with repeat PFTs and CT chest. She denied any changes in symptoms. PFTs also were unchanged from those done 3 months prior.  However, CT chest did look slightly worse with increased markings in the upper lobes.

She continued inhaled GM-CSF for another 3 months and sputum cultures for AFB, Nocardia and other pathogens were negative. After consulting with National Jewish Physicians, she was started on Mycophenolate mofetil orally advanced to the maximum dose of 3 gm/day. She has done well with improvement in her cough, lung function, six minute walk tests and CT scans and has not needed further whole lung lavage.  There are currently no reports of using this drug in this condition and thus it warrants further study for proof of benefit. Our patient has done well thus far, but there is also a case report of Mycophenolate actually causing PAP when used as an immunosuppressant in a patient with Wegener’s Granulomatosis so caution when using this is advised.¹⁸

References

1. Shah, PL, Hansell, D, Lawson, PR, et al. Pulmonary alveolar proteinosis: Clinical aspects and current concepts on pathogenesis. Thorax 2000; 55:67.

2. Kariman, K, Kylstra, JA, Spock, A. Pulmonary alveolar proteinosis: Prospective clinical experience in 23 patients for 15 years. Lung 1984; 162:223.

3. Milleron, BJ, Costabel, U, Teschler, H, et al. Bronchoalveolar lavage cell data in alveolar proteinosis. Am Rev Respir Dis 1991; 144:1330.

4. Inoue, Y, Trapnell, BC, Tazawa, R, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med 2008; 177:752.

5. Claypool, WD, Rogers, RM, Matuschak, GM. Update on the clinical diagnosis, management, and pathogenesis of pulmonary alveolar proteinosis (phospholipidosis). Chest 1984; 85:550.

6. Larson, RK, Gordinier, R. Pulmonary alveolar proteinosis. report of six cases, review of the literature, and formulation of a new theory. Ann Intern Med 1965; 62:292.

7. Beccaria, M, Luisetti, M, Rodi, G, et al. Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis. Eur Respir J 2004; 23:526.

8. Seymour, JF, Dunn, AR, Vincent, JM, et al. Efficacy of granulocyte-macrophage colony-stimulating factor in acquired alveolar proteinosis [letter]. N Engl J Med 1996; 335:1924.

9. Barraclough, RM, Gillies, AJ. Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. Thorax 2001; 56:664.

10. De Vega, MG, Sanchez-Palencia, A, Ramirez, A, et al. GM-CSF therapy in pulmonary alveolar proteinosis. Thorax 2002; 57:837.

11. Kavuru, MS, Sullivan, EJ, Piccin, R, et al. Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2000; 161:1143.

12. Venkateshiah, SB, Yan, TD, Bonfield, TL, et al. An open-label trial of granulocyte macrophage colony stimulating factor therapy for moderate symptomatic pulmonary alveolar proteinosis. Chest 2006; 130:227.

13. Seymour, JF, Doyle, IR, Nakata, K, et al. Relationship of anti-GM-CSF antibody concentration, surfactant protein A and B levels, and serum LDH to pulmonary parameters and response to GM-CSF therapy in patients with idiopathic alveolar proteinosis. Thorax 2003; 58:252.

14. Parker, LA, Novotny, DB. Recurrent alveolar proteinosis following double lung transplantation. Chest 1997; 111:1457.

15. Kavuru, MS, Bonfield, TL, Thomassen, MJ. Plasmapheresis, GM-CSF, and alveolar proteinosis. Am J Respir Crit Care Med 2003; 167:1036.

16. Borie, R, Debray, MP, Laine, C, et al. Rituximab therapy in autoimmune pulmonary alveolar proteinosis. Eur Respir J 2009; 33:1503.

17.  Kavuru MS, Malur A, Marshall I, Barna BP, Meziane M, Huizar I, Dalrymple H, Karnekar R, Thomassen MJ. An Open-Label Trial of Rituximab Therapy in Pulmonary Alveolar Proteinosis. Eur Respir J. Published on April 8, 2011 as doi: 10.1183/09031936.00197710.

18. Shah S, Phan N, Goyal G, Sharma G. Pulmonary Alveolar Proteinosis in a 67-Year-Old Woman with Wegener’s Granulomatosis. J Gen Intern Med. 2010; 25:1105.

Relationship between the Veterans Healthcare Administration Hospital Performance Measures and Outcomes

Richard A. Robbins, M.D.¹

Richard Gerkin, M.D.²

Clement U. Singarajah, M.D.¹

¹Phoenix Pulmonary and Critical Care Medicine Research and Education Foundation and ²Banner Good Samaritan Medical Center, Phoenix, AZ

Reference as: Robbins RA, Gerkin R, Singarajah CU. Relationship between the Veterans Healthcare Administration hospital performance measures and outcomes. Southwest J Pulm Crit Care 2011;3:92-133. (Click here for PDF version of manuscript)

Abstract

Health care organizations have been using performance measures to compare hospitals. However, it is unclear if compliance with these performance measures results in better healthcare outcomes. We examined compliance with acute myocardial infarction, congestive heart failure, pneumonia and surgical process of care measures with traditional outcome measures including mortality rates, morbidity rates, length of stay and readmission rates using the Veterans Healthcare Administration Quality and Safety report. Disappointingly, increased compliance with the performance measures was not correlated with better outcomes with the single exception of improved mortality with higher rates of compliance with echocardiography. We also evaluated the hospital level of care and found that higher levels of complexity of care correlated with the acute myocardial infarction performance measure, but not with the congestive heart failure, pneumonia, or surgical process of care performance measures.  However, level of complexity of care strongly correlated with all cause mortality (p<0.001), surgical mortality (p=0.037) and surgical morbidity (p=0.01). These data demonstrate that compliance with the performance measures are not correlated with improved healthcare outcomes, and suggest that if measures are used to compare hospitals, different measures need to be developed.

Introduction

The Joint Commission recently released “Improving America’s Hospitals: The Joint Commission’s Annual Report on Quality and Safety 2011 (1).  In this report the results of hospital compliance with the Joint Commission’s performance measures are listed. The Joint Commission announced not only is compliance improving but identified 405 hospitals as their “Top Performers on Key Quality Measures Program”. In a letter at the beginning of the report Mark Chassin, President of the Joint Commission, said “This program is designed to be an incentive for better performance on accountability measures and to support organizations in their quest to do better”.

However, there have been several criticisms of the report. First, many hospitals which were recognized as top hospitals by US News & World Report, HealthGrades Top 50 Hospitals, or Thomson Reuters Top Cardiovascular Hospitals were not included (2). Small community hospitals were overrepresented and large academic medical centers were underrepresented in the report. Chassin commented that this should be "a wake-up call to larger hospitals to put more resources into these programs…”. This is surprising since teaching hospitals, which are usually large, urban hospitals, have previously been reported to have lower risk-adjusted mortality rates and lengths of stay (3). Second, it has been pointed out that many of the performance measures are not or only weakly associated with traditional outcomes such as mortality (4-7). Therefore, we compared the compliance with the Joint Commission performance measures compared to mortality rates, morbidity rates, length of stay and readmissions using the Nation’s largest healthcare system, the Department of Veterans Affairs. The results demonstrate that compliance with performance measures are not correlated with improved outcomes.

Methods

The study was approved by the Western IRB.

Process Performance Measures. We evaluated hospital performance based on publicly available data from the 2010 VHA Facility Quality and Safety Report (9). These measures evaluate quality of care for acute myocardial infarction, congestive heart failure, pneumonia and surgical care improvement program (SCIP) during fiscal year 2009. For each of the measures, a hospital’s performance is calculated as the proportion of patients who received the indicated care out of all the patients who were eligible for the indicated care. The quality indicators are based on, and in most cases identical to those used for the Joint Commission’s Hospital Compare (acute myocardial infarction-Appendix 1; congestive heart failure-Appendix 2; pneumonia-Appendix 3, surgical quality-Appendix 4). Data were also available for each component of the congestive heart failure quality measure (see Appendix 2) which was evaluated independently.

Disease specific mortality. Hospital-specific, risk-standardized rates of mortality within 30 days of discharge are reported for patients hospitalized with a principal diagnosis of heart attack, heart failure, and pneumonia. For each condition, the risk-standardized (also known as "adjusted" or "risk-adjusted") hospital mortality rate are calculated using mathematical models that use administrative data to adjust for differences in patient characteristics that affect expected mortality rates (10).

Surgical morbidity and mortality. VA’s Surgical Quality Improvement Program (VASQIP) monitors major surgical procedures performed at VHA facilities and tracks risk adjusted surgical complications (morbidity) and mortality rates. Patient data are collected at each facility by a specially trained nurse and entered into the VA’s electronic health record: detailed preoperative patient characteristics including chart-abstracted medical conditions, functional status, recent laboratory tests, information about the surgical procedure performed, and 30-day outcomes data.

The VASQIP program analyzes these patient data using mathematical models to predict an individual patient’s expected outcome based on the patient’s preoperative characteristics and the type and nature of the surgical procedure. Overall patient outcomes for major surgical procedures are expressed by comparing observed rates of mortality and morbidity to the expected rates for those patients undergoing the procedure as observed-to-expected (O/E) ratios. For example, if, based on patient characteristics, a facility expected 5 deaths following major surgery, but only 4 patients died, the O/E ratio would be reported as 0.8.

Medical Surgical Length of Stay (LOS). These data are the VA hospital average length of stay for patients who were discharged from acute medicine or surgery bed sections. It does not include patients discharged from observation beds or discharged from other areas of the hospital such as mental health.

Readmission rates. A readmission was defined as a patient who has had a recent hospital stay and needs to re-enter the hospital again within 30 days. These rates are not adjusted for patient characteristics that affected expected admission rates, so comparisons among hospitals should be interpreted with caution.

CHF readmissions were reported separately. CHF readmission is defined by patients who had an initial hospitalization for CHF and were readmitted at least once to acute care in the hospital within 30 days following discharge for CHF.

Hospital level of care. For descriptive purposes, hospitals were grouped into levels of care. These are classified into 4 levels: highly complex (level 1); complex (level 2); moderate (level 3), and basic (level 4). In general, level 1 facilities and some level 2 facilities represent large urban, academic teaching medical centers.

Correlation with Outcomes. Pearson’s correlation coefficient was used to assess the correlation of compliance with the performance measures and outcomes. Significance was defined as p<0.05. For comparisons among hospital levels, ANOVA or Kruskall-Wallis testing was done, as appropriate.

Results

Disease specific and all cause mortality rates compared to performance measures. Hospital-specific, risk-standardized rates of mortality within 30 days of discharge for patients hospitalized with a principal diagnosis of heart attack, heart failure, and pneumonia were compared to performance measure compliance. There was no correlation (Table 1, p>0.05 all conditions) but with an increased incidence of pneumonia actually weakly correlating with higher compliance with the pneumonia performance measures (Table 1, p=0.0411). Furthermore, there was no correlation between all cause mortality and the average of the three compliance measures (Table 1, p>0.05). Because each table is large, only the correlation coefficients are presented in the text. The table data on which the correlations are based are given at the end of the manuscript. (N=the number of hospitals. NA=not available).

Table 1. Disease Specific Mortality Correlated with Performance Measure Compliance

Correlation Coefficients	r value	N	p value
Acute Myocardial Infarction Mortality and AMI Performance Measure	0.0266	103	0.7897
Congestive Heart Failure Mortality and CHF Performance Measure	0.0992	123	0.2752
Pneumonia Mortality and Pneumonia Performance Measure	0.1844	123	0.0411
All Cause Mortality vs. Average of Performance Measures	0.1118	122	0.2202

Each component of the congestive heart failure performance measure was evaluated individually. Performance of echocardiography correlated with improved mortality (Table 2, p=0.0496) but there was no correlation with use of a angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at discharge, discharge instructions, nor smoking cessation advice (Table 2, p>0.05 all comparisons).

Table 2. Heart Failure Mortality Correlated with Compliance to Individual Heart Failure Performance Measures

Correlation Coefficients	r value	N	p
ACEI or ARB	-0.1007	112	0.2908
Smoking Cessation	0.0651	112	0.4953
Discharge Instructions	0.1411	111	0.1396
Echocardiography	-0.1860	112	0.0496

Surgical mortality and morbidity rates compared to surgical performance measures. There was no correlation between compliance with the surgical care improvement program (SCIP) and surgical mortality or morbidity (Table 3, p>0.05 both comparisons).

Table 3. Surgical Care Improvement Program (SCIP) Compliance Correlated with Observed/Expected (O/E) Morbidity/Mortality

Correlation Coefficients	r value	N	p value
O/E Mortality	0.0943	99	0.3530
O/E Morbidity	0.0031	99	0.9757

Length of Stay. None of the performance measures correlated with medical-surgical length of stay (Table 4, p>0.05 all comparisons).

Table 4. Length of Stay (LOS) Correlated with Performance Measure Compliance

Correlation Coefficients	r value	N	p value
LOS compared to AMI	0.1047	103	0.2926
LOS compared to CHF	-0.0178	123	0.8451
LOS compared to Pneumonia	-0.1679	123	0.0634
LOS compared to SCIP	-0.0404	106	0.6809
LOS compared to Average	0.0028	123	0.9755

Readmission rates. There was no correlation between all cause readmission rates and the acute myocardial infarction, congestive heart failure, pneumonia or surgical performance measures (Table 5, p>0.05 all comparisons). There was no correlation between heart failure readmission rate and the heart failure performance measure (data not shown, r=0.1525, p=0.0921).

Table 5. Readmission Rate Correlated with Performance Measure Compliance

Correlation Coefficients
	r value	N	p
AMI	0.1688	103	0.0883
CHF	0.1505	123	0.0966
Pneumonia	0.0581	123	0.5233
Average	0.1281	122	0.1597

Hospital level of care. Acute myocardial infarction performance measures inversely correlated with the hospital level of care, i.e., the higher the hospital complexity level, the better the compliance (Table 6, p=0.004). However, there was no correlation between congestive heart failure, pneumonia, surgical care improvement program or the average of the measures and the hospital level of care (Table 6).

Table 6. Hospital Level Correlated with Performance Measure Compliance

ANOVA	N	p
Acute Myocardial Infarction (AMI)	103	0.004
Congestive Heart Failure (CHF)	120	0.782
Community Acquired Pneumonia	120	0.296
Surgical Care Improvement Program (SCIP)	106	0.801
Average of Process of Care Measures	120	0.285

There was no correlation between the level of hospital care and the acute myocardial infarction, congestive heart failure, nor pneumonia mortality (Table 7, p>0.05 all comparisons). However, there was a strong correlation between all cause morality (p<0.001) and a correlation between surgical Observed/Expected mortality (Table 7, p=0.037) and surgical Observed/Expected morbidity (p=0.010).

Table 7. Hospital Level Correlated with Mortality and Surgical Morbidity

ANOVA	N	p
Acute Myocardial Infarction (AMI) Mortality	103	0.835
Congestive Heart Failure (CHF) Mortality	120	0.493
Pneumonia Mortality	120	0.547
All Cause Mortality	106	<0.001
Surgical O/E Mortality	99	0.037
Surgical O/E Morbidity	99	0.010

Discussion

These data from the Nation’s largest healthcare system demonstrate that increasing compliance of the performance measures prescribed by the Joint Commission does not affect disease specific mortality, all cause mortality, surgical mortality, surgical morbidity, length of stay or readmissions with the single exception of improved mortality correlating with increased compliance with performance of echocardiography. In contrast to the Joint Commission’s list of top hospitals which found smaller and rural hospitals to be overrepresented, we found that only the acute myocardial infarction performance measure correlated with a higher level of hospital care which represents mostly large, urban hospitals. We did find that all cause mortality and surgical morbidity highly correlated with the level of care. This would appear to differ from the Joint Commission’s list of top hospitals which tended to be small and rural, since VA hospitals with higher levels of care largely represent large urban, academic teaching medical centers.

There are multiple possible reasons for the lack of correlation between the performance measures and outcomes. Many of the outcomes are evidence based but several are not. For example, there are no randomized, multi-center studies evaluating the efficacy of discharge instructions, smoking cessation advice and pneumococcal vaccination. Studies with discharge instructions are retrospective, observational studies and have largely not shown improved outcomes (11,12). Several meta-analyses have failed to demonstrate the efficacy of pneumococcal vaccine in adults (13-15). Advice to quit smoking without follow up support or pharmacologic intervention has not been shown to lower smoking cessation rates (16). Mandating ineffective interventions such as these would not be expected to have a positive effect on outcomes. However, this is where most of the improvement in performance measure outcome has occurred (2).

Most of the interventions are grouped or bundled. Lack of compliance with any one of the bundle is taken as noncompliance with the whole. However, if the only difference between hospitals is noncompliance with an ineffective performance measure, there would not be any expected improvement in outcomes.

Many of the strongly evidence-based outcomes have very high compliance, usually exceeding 95% (9). It is possible that small improvements of 1 or 2% in effective performance measures might have too small an impact on outcomes to be detected even in large databases such as the Veterans Administration which examined 485,774 acute medical/surgical discharges in 2009.

The performance measures appear to avoid highly technical or costly interventions and often avoid interventions which have been shown positively affect outcomes. For example, beta blockers and spironolactone have been shown to be effective in heart failure but are not included in the congestive heart failure performance measures (17,18). Furthermore, carvedilol has been shown to be superior to metoprolol in improving survival (19). Why the performance measures include use of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker but not carvedilol and spironolactone is unclear.

Some of the performance measures may have caused inadvertent harm. For example, administration of antibiotics within 4 hours to patients with pneumonia was a previous performance measure. However, studies showed that this performance measurement led to administration of antibiotics in many patients who proved not to have pneumonia or another infectious disease, and a systematic review concluded that “evidence from observational studies fails to confirm decreased mortality with early administration of antibiotics in stable patients with [community acquired pneumonia]”  (20-22). The time has since been changed to 6 hours, but it is unclear if that it is any better than the initial 4 hour timing used (7).

We did not confirm the Joint Commission’s findings that the top hospitals are overrepresented by small, rural hospitals. We found no correlation between hospital level of complexity of care and performance measure compliance with the exception of acute myocardial infarction which was higher in hospitals with higher complexities of care. Although we found no correlation of the performance measures with any outcome measures, we did find a strong correlation between the hospital level of complexity of care and overall survival and surgical morbidity with the hospitals having the higher level of complexity having improved survival and decreased surgical morbidity. This would seem consistent with concept that volume of care correlates with outcomes.

It seems surprising that initiation of performance measures seem to go through such little scrutiny. In a 2005 editorial Angus and Abraham (23) addressed the issue of when there is sufficient evidence for a concept to be widely applied as a guideline or performance measure. Comparing guidelines to evaluation of novel pharmacologic therapies, they point out that promising phase II studies are insufficient for regulatory approval. Instead, one, and usually two, large multicenter phase III trials are necessary to confirm reliability. The same principle is echoed in evidence-based medicine, where grade A recommendations are based on two or more large, positive, randomized, and multicenter trials. This seems a reasonable suggestion. Perhaps what is needed is an independent Federal or private agency to review and approve performance measures, and as Angus and Abraham suggest, require at least two randomized, multicenter trials before implementation

The data presented in this manuscript do not support the usefulness of increasing compliance with the Veterans Administration’s (or the Joint Commission’s) performance measures in improving outcomes such as mortality, morbidity, length of stay or readmission rates. Until compliance with the performance measures results in improved outcomes, investment to improve these performance measures seems to be a poor utilization of resources. It suggests that oversight of regulatory agencies is needed in developing and implementing performance measures. If performance measures are to be used, new, clinically meaningful measures that correlate with outcomes need to be developed. 

References

1. Available at: http://www.jointcommission.org/accreditation/hospitals.aspx (accessed 9-25-11).
2. Available at: http://www.forbes.com/sites/davidwhelan/2011/09/20/is-the-joint-commission-list-of-top-hospitals-worth-heeding/ (accessed 9-25-11).
3. Rosenthal GE, Harper DL, Quinn LM. Severity-adjusted mortality and length of stay in teaching and nonteaching hospitals. JAMA 1997;278:485-90.
4. Werner RM, Bradlow ET. Relationship between Medicare's hospital compare performance measures and mortality rates. JAMA 2006;296:2694-702.
5. Peterson ED, Roe MT, Mulgund J, DeLong ER, Lytle BL, Brindis RG, Smith SC Jr, Pollack CV Jr, Newby LK, Harrington RA, Gibler WB, Ohman EM. Association between hospital process performance and outcomes among patients with acute coronary syndromes. JAMA 2006;295:1912-20.
6. Fonarow GC, Yancy CW, Heywood JT; ADHERE Scientific Advisory Committee, Study Group, and Investigators. Adherence to heart failure quality-of-care indicators in US hosptials: analysis of the ADHERE Registry. Arch Int Med 2005;165: 1469-77.
7. Wachter RM, Flanders SA, Fee C, Pronovost PJ. Public reporting of antibiotic timing in patients with pneumonia: lessons from a flawed performance measure. Ann Intern Med 2008;149:29-32.
8. Stulberg JJ, Delaney CP, Neuhauser DV, Aron DC, Fu P, Koroukian SM.  Adherence to surgical care improvement project measures and the association with postoperative infections. JAMA. 2010;303:2479-85.
9. Available at: http://www.va.gov/health/docs/HospitalReportCard2010.pdf (accessed 9-28-11).
10. Ross JS, Maynard C, Krumholz HM, Sun H, Rumsfeld JS, Normand SL, Wang Y, Fihn SD. Use of administrative claims models to assess 30 day mortality among Veterans Health Administration hospitals. Medical Care 2010; 48: 652-658.
11. VanSuch M, Naessens JM, Stroebel RJ, Huddleston JM, Williams AR. Effect of discharge instructions on readmission of hospitalised patients with heart failure: do all of the Joint Commission on Accreditation of Healthcare Organizations heart failure core measures reflect better care? Qual Saf Health Care 2006;15:414-7.
12. Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, O'Connor CM, Pieper K, Sun JL, Yancy C, Young JB; OPTIMIZE-HF Investigators and Hospitals. Association between performance measures and clinical outcomes for patients hospitalized with heart failure. JAMA 2007;297:61-70.
13. Fine MJ, Smith MA, Carson CA, Meffe F, Sankey SS, Weissfeld LA, Detsky AS, Kapoor WN. Efficacy of pneumococcal vaccination in adults. A meta-analysis of randomized controlled trials. Arch Int Med 1994;154:2666-77.
14. Dear K, Holden J, Andrews R, Tatham D. Vaccines for preventing pneumococcal infection in adults. Cochrane Database Sys Rev 2003:CD000422.
15. Huss A, Scott P, Stuck AE, Trotter C, Egger M. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ 2009;180:48-58.
16. Rigotti NA, Munafo MR, Stead LF. Smoking cessation interventions for hospitalized smokers: A systematic review. Arch Intern Med 2008;168:1950-1960.
17. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med 1998;339:489-97.
18. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-17.
19. Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A. Carvedilol Or Metoprolol European Trial Investigators. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7-13.
20. Kanwar M, Brar N, Khatib R, Fakih MG. Misdiagnosis of community acquired pneumonia and inappropriate utilization of antibiotics: side effects of the 4-h antibiotic administration rule. Chest 2007;131:1865-9.
21. Welker JA, Huston M, McCue JD. Antibiotic timing and errors in diagnosing pneumonia. Arch Intern Med 2008;168:351-6.
22. Yu KT, Wyer PC. Evidence-based emergency medicine/critically appraised topic. Evidence behind the 4-hour rule for initiation of antibiotic therapy in community-acquired pneumonia. Ann Emerg Med 2008;51:651-62.
23. Angus DC, Abraham E. Intensive insulin therapy in critical illness: when is the evidence enough? Am J Resp Crit Care 2005;172:1358-9

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Congenital Bronchial Atresia: A Case Report with Radiographic and Pathologic Correlation

Lewis J. Wesselius, MD1

John R. Muhm, MD2

Henry D. Tazelaar, MD3

Departments of Pulmonary Medicine1, Radiology2, and Laboratory Medicine- Pathology3, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259

Reference as: Wesselius LJ, Muhm JR, Tazelaar HD. Congenital bronchial atresia: a case report with radiographic and pathologic correlation. Southwest J Pulm Crit Care 2011;3:64-9. (Click here for a PDF version)

Abstract

Bronchial atresia is a rare congenital disorder characterized by localized atresia or stenosis of a segmental bronchus.  Imaging features typically include mucus impaction in distal airways associated with regional lung hyperlucency. Pathologic features of bronchial atresia have been rarely been reported.  This case demonstrates CT features of this disorder as well as the unusual finding of increased lung uptake of 18F-fluorodeoxyglucose on PET scan.  This finding led to a surgical lung biopsy to exclude infectious or neoplastic disorders.  This case provides radiologic-pathologic correlation in a patient with congenital bronchial atresia and demonstrates that localized, mildly increased uptake on PET scan be associated bronchial atresia.

Case Presentation

A 35-year-old woman was referred for evaluation of an abnormal thoracic CT scan.     An abnormality was noted on a routine chest radiograph 2 years previously, and thoracic CT reportedly showed an “infiltrate” in the right upper lobe.  Bronchoscopy with bronchoalveolar lavage performed 1 year previously was reportedly negative.  The patient was asymptomatic and denied any cough, fever or shortness of breath.  On physical examination the patient was afebrile and the chest examination was within normal limits.  She had a normal complete blood count and serologic studies for coccidioidomycosis were negative.  A recent chest radiograph (Figure 1) and thoracic CT (Figure 2) performed at the referring medical center demonstrated abnormalities in the right upper lobe, without clear visualization of the posterior segment right upper lobe bronchus. Repeat bronchoscopy was performed which and reportedly demonstrated a patent right upper lobe posterior segmental bronchial orifice, although limited visualization into the airway was noted.  Microbiologic studies and cytologic examination of the bronchoalveolar lavage fluid were negative.

Figure 1:   Chest radiograph performed one month prior to presentation shows small nodular opacities of indeterminate etiology in the right upper lung.

Figure 2:  Thoracic CT shows atresia of the central portion of the right upper lobe posterior segment bronchus (arrow).  In the right upper lobe posterior segment, peripheral to the atretic bronchus, numerous irregular opacities resulting from dysplastic bronchi filled with mucus are noted.  The hypoattenuating areas in the right upper lobe posterior segment represent hypoperfused secondary pulmonary lobules resulting from the obstructed, dysplastic bronchioles.

Subsequent Clinical Course

Subsequent 18F-fluorodeoxyglucose positron emission tomography (FDG- PET, Figure 3) scan performed at the outside medical center showed hypermetabolism within the right upper lobe, with a standard uptake value (SUV) of 2.9.

Figure 3: Image from Coronal FDG-PET shows areas of mild-to-moderate increased uptake (SUV 2.2) in the posteromedial aspect of the right upper lobe.

The finding of elevated FDG uptake on PET scan, as well as an increase in the extent of CT abnormalities, raised clinical concern for an undiagnosed infectious process or low-grade malignancy. The patient subsequently underwent a thoracoscopic lung biopsy at the outside institution to exclude those possibilities.

Further radiology review of the lung CT scan was concurrently requested by the referring physician and the radiographic features of bronchial atresia involving the posterior segment of the right upper lobe were noted.  There was a dysplastic bronchus supplying the posterior segment of the right upper lobe, filled with mucus, and associated with evidence of hypoperfusion of that segment.  Review of the tissue obtained at lung biopsy (Figure 4) demonstrated mucus impaction in small airways, consistent with changes secondary to bronchial atresia.  There was no evidence of active infection or a neoplastic process.

Figure 4: VATS biopsy specimen obtained from the right upper lobe.  The biopsy shows a chronic bronchiolitis (a) with lymphoid hyperplasia and germinal centers (b.center). There is also prominent bronchiolectasis (c) with mucostasis in the airway lumen and extending into the surrounding lung (d).

Discussion

Bronchial atresia is an uncommon congenital tracheobronchial abnormality first described in 1953 and is characterized by stenosis of a segmental airway (1). The abnormality generally involves a single segment, although cases with mult- isegment involvement have been reported (2).  The apical-posterior segment of the left upper lobe is most frequently involved, followed by segments within the right upper, middle and lower lobes (3,4).  This abnormality is frequently asymptomatic and is incidentally detected on chest radiography in 58% of cases (2). Patients may present, often in early adulthood, with symptoms of recurrent infections (21%), dyspnea (14%) and cough (6%). Cases associated with spontaneous pneumothorax have been reported (5).

The diagnosis of congenital bronchial atresia can generally be made from thoracic CT findings alone. Characteristic imaging findings include mucus impaction in dilated airways distal to the area of stenosis (6), typically associated with  regional pulmonary parenchymal hyperlucency due to hypoperfusion, representing mosaic perfusion, resulting from obstructed dysplastic bronchi.

Bronchoscopy can be helpful to exclude competing diagnostic considerations and to exclude infectious processes.  In some patients, segmental airway atresia or an obvious narrowing may be directly observed at bronchoscopy.  However, the area of stenosis is not always visible at bronchoscopy (7). In our patient, the bronchoscopy did not clearly identify an area of segmental narrowing, although that finding was suggested by the CT scan (Figure 2).

FDG-PET (Figure 3), performed to evaluate for a possible undiagnosed infectious or malignant process, showed increased uptake in the areas of radiographic abnormality.      However, subsequent VATS biopsy of the right upper lobe was negative for any infectious or neoplastic process.  Increased uptake pulmonary parenchymal on FDG-PET scan is commonly seen in lung neoplasms and infections, but has also been reported in non-infectious inflammatory lung conditions, including sarcoidosis and idiopathic pulmonary fibrosis (8,9).  There are prior case reports of localized pulmonary parenchymal uptake on FDG-PET scans performed in patients with benign airway disorders, including acute bronchitis and allergic bronchopulmonary aspergillosis (10,11).  The finding of increased uptake on FDG-PET scan has not previously been reported in patients with congenital bronchial atresia.  The specific reason for the localized uptake in the pulmonary parenchyma distal to the atretic bronchus in our patient is not certain. It is possible that local inflammation associated with mucostasis contributed to this finding as there was some evidence of interstitial inflammation noted on the surgical lung biopsy.

The lung biopsy obtained in this patient showed findings consistent with bronchial atresia including mucostasis in airways. The finding of mucostasis correlates with the CT findings of mucus impaction in dilated airways.  Review of the literature indicated only one prior report of pathologic findings in patients with bronchial atresia (12). The findings in our case- respiratory bronchioles plugged with mucus- are consistent with those previously reported. Dilation of surrounding alveoli without evidence of destruction has also been previously reported, consistent with air-trapping.

Summary

Congenital bronchial atresia is an uncommon disorder that can present with a specific pattern on thoracic CT performed on asymptomatic patients or patients with respiratory symptoms of recurrent infections, dyspnea and cough. Bronchoscopy can be helpful to exclude other diagnostic considerations and may demonstrate evidence of segmental bronchial stenosis, although the area of stenosis may not be evident in all cases. Our patient presented with the unusual finding of mildly increased, localized uptake of FDG-PET scan, a finding previously unreported.  Lung biopsy confirmed pathologic features consistent with bronchial atresia, including airway dilatation and terminal bronchial mucus impaction.

References

1. Ramsey BH, Byron FX.  Mucocele, congenital bronchiectasis and bronchogenic cyst. J. Thoracic Surg 1953;26:21-30.
2. Jederlinic PJ, Sicilian L, Baigelman W, et al.  Congenital bronchial atresia – a report of 4 cases and a review of the literature.  Medicine 1986;65:73-83.
3. Meng RL, Jensik RJ, Faher LP, Matthew GP, Kittle CF.  Bronchial atresia, Ann Thoracic Surg 1978;25:184-192.
4. Muller NL, Fraser RS, Colman N, Pare P.  Developmental and hereditary lung disease.  In: Radiologic diagnosis of diseases of the chest.  Philadelphia, PA: Saunders; 2001: 125-128.
5. Berkman N, Bar-Ziv J, Breuer R.  Recurrent spontaneous pneumothorax associated with bronchial atresia.  Resp Med 1996;90:307-309.
6. Matsushima H, Takoyanagi N, Satoh M, et al.  Congenital bronchial atresia: radiologic findings in nine patients.  J Comp Assist Tomog  2002;26:860-864.
7. Ward S. Morcos SK. Congenital bronchial atresia – presentation of three cases and a pictoral review.  Clin Radiol 1999;54:144-148.
8. Brudin LH, Balind SO, Rhodes CG, et al.  Fluorine-18 deoxyglucose uptake in sarcoidosis measured with positron emission tomography.  Eur J Nucl Med 1994;21:297-305.
9. Groves Am, Win T, Screaton NJ, et al.  Idiopathic pulmonary fibrosis and diffuse parenchymal lung disease: implications from initial experience with18F-FDG PET/CT. J Nucl Med 2009;50:538-545.
10. Kicska G, Zhuang H, Alavi H.  Acute bronchitis imaged with F-18 FDG positron emission tomography.  Clin Nucl Med 2003;28:511-512.
11. Nakajima H, Sawaguchi H, Hoshi S, Nakajimo S, Tohda Y.  Intense 18F- fluorodeoxyglucose uptake due to allergic bronchopulmonary aspergillosis. Jap J. Allergology 2009;58:1426-32.
12. Gipson MG, Cummings KW, Hurth KM. Bronchial atresia  Radiographics 2002;29:1531-1535.

Pulmonary Nocardiosis and Empyema in a Patient with Metastatic Neuroendocrine Tumor

Nimesh K. Patel, DO

Linda Snyder, MD

University of Arizona, Department of Medicine. Tucson, Arizona

Reference as: Patel NK, Snyder L. Pulmonary nocardiosis and empyema in a patient with metastatic neuroendocrine tumor. Southwest J Pulm Crit Care 2011;3:28-33. (Click here for a PDF version)

Abstract

Nocardia is a ubiquitous aerobic gram-positive bacterium that can cause local or disseminated infection. Nocardiosis involves the lung in the majority of cases. Nocardiosis is often an opportunistic infection, but can also affect non-immunocompromised hosts. This case report highlights the presence of empyema due to Nocardia cyriacigeorgica infection, an unusual feature of Nocardia pulmonary involvement. 

Case Presentation

History of Present Illness: A 65 year-old male with a history of metastatic neuroendocrine tumor of the pancreas, was admitted to the hospital with a one-week history of hemoptysis, cough, and dyspnea. He was treated for presumed community acquired pneumonia with moxifloxacin two weeks prior to admission. He was receiving monthly octreotide injections for treatment of the neuroendocrine tumor. The patient had no history of corticosteroid use.  

Physical examination:

Vital signs: Temperature 99.9F, Respirations18, Blood Pressure 104/69, Pulse 96, SaO2 91% on oxygen at 2 liters per minute by nasal cannula

General: The patient was in no acute distress. He was alert and oriented to person, place and time.

HEENT: No significant abnormalities.

Chest: Dullness to percussion, mid-lower right thoracic cavity, with scattered crackles. 

Cardiovascular: regular rate, normal S1 and S2, no murmurs appreciated.  Abdomen: positive bowel sounds, soft, non-tender, non-distended, positive hepatosplenomegaly. 

Extremities: +2 pitting edema bilaterally extending to mid-thigh level

Laboratory and radiographic findings: The peripheral white blood cell count was 8, 000 cell/mm³ with a differential as follows 91% neutrophils/bands, 7% lymphocytes, 1% myelocyte, 1% reactive lymphocyte, hemoglobin was 11 g/dL and the platelet count was normal. The basic metabolic panel revealed blood urea nitrogen of 30 mg/dl and creatinine of 1.5 mg/dl. The hepatic panel was normal except for an elevated alkaline phosphatase of 530 IU/L. Coccidioides IgM and IgG serology performed by immunodiffusion were negative.

The chest radiographs from two weeks prior to admission (Figure 1), admission (Figure 2) and admission computerized tomography of the chest (Figure 3) are shown.  

Figure 1. Chest radiograph two weeks before admission:  Right middle lobe consolidation with volume loss and small right pleural effusion

 

Figure 2.  Chest radiograph on admission: Increasing patchy opacifications involving the right upper lobe, right middle lobe, and left lower lobe, with cavity formation noted in the left lung. There is right paratracheal lymphadenopathy noted.

Figure 3: Computerized tomography of the chest showing multifocal consolidation with a necrotizing process containing central lucencies. A loculated, moderate sized right anterior pleural effusion with lucencies is compatible with an empyema.

Hospital course:

Our patient was started on broad-spectrum antimicrobial therapy and underwent chest tube drainage of the loculated effusion.  A sputum gram stain revealed 4+ weakly acid-fast branching bacilli, consistent with Nocardia. The gram stain of the pleural fluid showed 3+ polymorphonuclear cells and 3+ gram-positive, branching, weakly acid-fast bacilli, consistent with Nocardia.  The culture from sputum and pleural fluid grew Nocardia cyriacigeorgica. 

Computerized tomography of the brain showed no intracranial abnormalities. The patient was treated with high dose trimethoprim/sulfamethoxazole, two double strength tablets three times a day with monitoring of sulfamethoxazole levels. The patient clinically improved with antimicrobial treatment and drainage of the empyema. The chest tube was successfully removed and the patient’s symptoms of cough and dyspnea resolved. A chest x-ray showed resolution of the right middle lobe and left lower lobe infiltrative process.

Figure 4.  Chest radiograph post-antimicrobial treatment: Interval resolution of right middle lobe and left lower lobe infiltrative process. Post infectious inflammatory changes are noted in the right middle lobe.

Discussion

Nocardiosis is an important opportunistic infection caused by aerobic actinomycetes in the genus Nocardia. Nocardia asteroides has been considered the most common species to cause human disease, however classification has become more complex with the use of molecular techniques. Species formerly included in the Nocardia asteroides complex are now considered distinct species.  Nocardia cyriacigeorgica is one of the more common isolates and has been noted to cause pleural disease and empyema.  Nocardia species are found in soil and can become airborne; the most common route of entry for infection is inhalation. Effective cell-mediated immunity of the host is crucial to combating infection with Nocardia species.  Two recent reviews of nocardiosis highlight important clinical features of this disease (1,2). The most common symptoms are fever, cough, pleuritic chest pain and headache. Specific risk factors for Nocardia infection are present in the majority of patients and include corticosteroid treatment and immunosuppression. Additional risk factors include malignancy and chronic lung disease. Of interest to pulmonologists, chronic obstructive pulmonary disease (COPD) was a common underlying condition, representing over 20% of patients with nocardiosis in these reports. Common chest radiographic presentations of pulmonary nocardiosis include consolidation, nodules and cavities. The diagnosis of pulmonary nocardiosis is made from sputum and bronchoalveolar lavage specimens in the majority of patients. In addition, recent reviews document that pleural effusions are present in up to 35% of patients with pulmonary nocardiosis.  In one report, when pleural fluid was sampled, Nocardia was isolated in the majority of patients. Nocardia cyriacigeorgica can cause invasive pulmonary disease and was found to be the predominant species in pulmonary nocardiosis in one review.

Summary

Nocardiosis is an important opportunistic pulmonary disease. The diagnosis should be included in the differential diagnosis of pulmonary infiltrates in immunosuppressed populations, including patients after organ transplantation, with advanced HIV infection and those receiving chronic corticosteroid therapy or chemotherapy. Radiographic findings of lung involvement are variable and include single or multiple nodules or cavities, alveolar or interstitial infiltrates, and pleural effusions. This case report highlights the unusual presentation of Nocardia cyriacigeorgica pulmonary infection with extensive cavitary parenchymal disease and concomitant empyema. 

References

1. Minero MV, et al. Nocardiosis at the Turn of the Century.  Medicine 2009;88:250-61.
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