J. Unresolved Pneumonia

Introduction

Unresolved pneumonia, especially in older patients, presents a problem to the primary care physician that doesn’t go away. Pneumonia strikes over 2,000,000 Americans annually, resulting in over 800,000 hospitalizations and 50,000 deaths. X-ray manifestations of many pneumonias fail to resolve in 30 days, requiring a decision as to the need for additional costly and potentially harmful evaluations. The workup can be straightforward or frustrating. The following approach is presented for practical resolution of unresolved pneumonias.

Infiltrates thought to be due to pneumonia must be followed to their radiologic resolution. Because most pneumonias are treated without identifying the etiology, the practitioner frequently does not know the extent of “normal” duration of resolution and therefore must depend on indirect information to infer the cause and natural history for a specific patient. Factors that influence the rate of resolution are listed in Table 19. The most important of these are age, host defenses, and comorbidities.

When one or more of these factors is present, it may be necessary to wait 6-8 weeks for resolution to occur, unless there are early clinical clues that raise the suspicion of an unusual infection or noninfectious process such as malignancy. If the causative organism is known, Table 20 may be useful for estimating the duration of resolution.

When radiologic resolution is not satisfactory, additional evaluations are needed and the various causes of unresolved infiltrates need to be considered (see Table 21).

Common Unresolved Pneumonias

A review of the most distinctive features of these pneumonias can be useful in eliciting clues to the identity and, therefore, the natural history of the infectious causes of unresolved infiltrates.

Pneumococcal Pneumonia: The pneumococcus causes the greatest number of unresolved pneumonias. Aspiration, often associated with sedation, is a very common cause. Delayed resolution is seen most often in the elderly and in cases associated with bacteremia. Eight to eleven weeks resolution time is often encountered. Residual atelectasis and pleural abnormalities are present at two months in about 1/3 of the elderly patients and in 10% of younger patients.

Staphylococcal Pneumonia: Staphylococcal pneumonia frequently follows influenza or other viral respiratory infections, is seen more frequently in the elderly, and is often the cause of hospital-acquired pneumonia, especially in patients with COPD. Bilateral lower lobe involvement and pleural effusions, often empyema, are common. Resolution of staphylococcal pneumonia may be expected to follow a prolonged course.

Hemophilus influenzae Pneumonia: Older patients with COPD and alcoholism are especially susceptible to this organism. The hospital course and eventual resolution are frequently prolonged.

Legionella Pneumonia: This pneumonia results from inhalation of airborne water contaminants or pharyngeal contents and occurs more often than originally believed. It is seen more frequently in smokers and in patients with chronic pulmonary, cardiac, renal and neoplastic disease. Twenty-five to fifty percent progress to multi-lobar involvement, and resolution of this pneumonia is one of the slowest of any community-acquired pneumonia. Residual fibrosis may occur in as many as one quarter of the cases. Complete resolution occurs in only 55% of the cases in twelve weeks. Unless other clinical information is of concern, follow up chest radiography at 6-8 weeks intervals is sufficient without significant risk of misdiagnosis.

Gram Negative Pneumonias: Nursing-home, elderly, and hospitalized patients are more commonly affected. Comorbidities such as COPD, neoplasm, diabetes mellitus, and bronchiectasis increase the risk for this type of pneumonia. Abscesses and residual fibrosis are common.

Viral Pneumonias: The elderly and the immunosuppressed are more susceptible to viral pneumonias. Superinfection with other organisms such as Staphylococcus aureus and Hemophilus influenzae is common. Even typical viral pneumonia may be associated with other diagnoses such as bronchiolitis obliterans with organizing pneumonia, bronchiectasis, and pulmonary fibrosis.

Mycobacterium tuberculosis Pneumonia: Immigrants from Africa, Latin America, and many countries of Asia have a higher incidence of tuberculosis than the general population of the United States. The presence of alcoholism, cavities and/or apical infiltrates are additional reasons to raise the suspicion of tuberculosis. As in other pneumonias, AIDS may alter the typical radiographic presentation of tuberculosis.

Noninfectious Causes of Unresolved Infiltrates

Neoplasm: Neoplasms are one of the most common and important causes of unresolved pneumonia. Patients with neoplasms presenting with pneumonia may have with stridor, wheezing, or sudden onset of marked shortness of breath. Hemoptysis occurs in 25-50% of cases. Smokers older than 45 years of age, especially with weight loss or recurrent pneumonia, should undergo additional workup. Obstructive endobronchial lesions may be primary malignant lesions, metastatic from breast, kidneys, or GI tract, or on occasion may be bronchial carcinoid tumors or papillomas. Cavitary lesions may signify a necrotizing neoplastic process. Bronchoalveolar cell carcinoma may present as lobar consolidation with air bronchograms resembling pneumonia.

Pulmonary Emboli: Pulmonary embolism with infarction can masquerade as pneumonia, occurring more commonly in older, immobilized, or obese patients, and in those with heart failure. These infiltrates are usually peripheral and resolve by shrinking slowly over several weeks.

Other Causes: A variety of unusual conditions may declare themselves as unresolved pneumonia. These include amyloid infiltrations, asbestos-induced round atelectasis, and various noninfectious granulomas (e.g., rheumatoid, Wegener’s, and bronchocentric).

Clinical Approach to Diagnosis

Figure 3 suggests an overall diagnostic approach to unresolved infiltrates. Chest x-rays that show persistent infiltrates need to be periodically evaluated to their satisfactory resolution. Once the estimated time for resolution of what was thought to be an infectious process has passed, one should proceed to a more detailed evaluation. This repeat assessment, as emphasized in Chapter 1, should include a search for previously unelicited symptoms, including complete travel, occupational, drug, and hobby history. Signs and symptoms of systemic diseases such as collagen vascular disease, rheumatoid arthritis, etc. may present clues to more obscure etiologies.

A persistent cough (see Section B), hemoptysis (Section C), fever, shortness of breath (Section D), weight loss, or chest pain necessitates a repeat chest film. Evaluation of the chest x-ray, however, is seldom helpful in identification of the cause of the nonresolution. Once the plain film identifies a problem, but not a cause, computed tomography is indicated to find possible cavities, masses, endobronchial lesions, adenopathy, effusions, or other abnormalities. At this point, referral to a specialist is recommended for consideration of further diagnostic procedures such as bronchoscopy, transbronchial biopsy, transthoracic needle aspiration, thoracoscopic lung biopsy, or open lung biopsy. Bronchoscopy can be diagnostic in up to 80% of the cases.

Other useful tests in selected patients are cultures and/or cytologic examination of sputum (expectorated or induced) and bronchoalveolar lavage fluid for mycobacteria and fungi. Thoracentesis is indicated in patients with accessible pleural effusions; other useful procedures include pleural biopsy or thoracoscopy.

The ultimate diagnostic procedure is thoracotomy with lung biopsy. When the suspicious lesion is peripherally located and where expertise and facilities are available, biopsy or even resection may be carried out by thoracoscopy.

When to Refer

Each practitioner has his or her own level of expertise, but when there is any doubt, a consultation is indicated. Examples are (1) when neoplasm is suspected and cannot be ruled out by noninvasive methods, (2) when unresolved densities require invasive procedures, and (3) when help is needed in treatment of obscure causes.

Medicolegal Concerns

• Failure to diagnose lung cancer is high on the list of causes for malpractice lawsuits. Maintain a high level of suspicion and a low threshold of referral for consultation.

• Unfortunately, tuberculosis is frequently overlooked. As in potentially neoplastic cases, having a high index of suspicion is very important, and when there is the slightest doubt, culture the sputum for mycobacteria or seek consultation.

• What appears to be pneumonia should be followed to resolution on the anticipated schedule. A histologic diagnosis of residual masses and dense infiltrates that suggest malignancy is commonly necessary. Make sure your patient knows that followup is mandatory and that diagnostic procedures may be needed.

• One should be very cautious with patients who fail to follow instructions and/or do not follow up with their appropriate evaluations. Explain thoroughly to the patient as well as the family the importance of following instructions exactly and returning for appropriate follow-up. Document completely all these conversations.

Summary

Unresolved radiographic densities can be approached in a systematic way that avoids unnecessary expense and risks to the patients. Knowledge of the natural history of the common pneumonias and the exercise of judgement as to when to refer are important aspects of the approach to these problems. Fortunately, most cases can be resolved without undue complications and expense. Refer when in doubt and be sure that appropriate follow-up is accomplished.

References

Niederman MS, Sarosi GA. Respiratory Infections. Philadelphia, W.B. Saunders Co. 1994; 277- 289. An excellent comprehensive text of practical importance.

Bartlett JG, Breiman RF, Mandell LA, File, TM Jr. Community-acquired pneumonia in adults: Guidelines for management. Clin Infect Dis 1998; 26:811-38. A discussion of current comprehensive guidelines in areas where there are still many unresolved controversies.

Kirkland SH. Chronic pneumonias. Sem Resp Inf 1998; 13:54-67. A detailed description of and a clinical approach to pneumonias that fail to resolve in one month.

Mitt RL, Schwab RJ, Duchin JS, et al. Radiographic resolution of community- acquired pneumonia. Am J Resp Crit Care Med 1994;149:630-635. A description of the radiographic history of community-acquired pneumonia.

Cabreros LJ, Rajendran R, Drimoussis A, et al. Delayed resolution of pneumonia. Postgrad Med 1995;99:151-158. Methods of prediction of estimated resolution time of the most common pneumonias.

Orens JB, Sitrin RG, Lynch JP. The approach to nonresolving pneumonia. Med Clin North America 1994;78 :1143-1172. A detailed review of the natural history, diagnosis, and treatment of non-resolved infiltrates.

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