The overdiagnosis of pneumonia

PNEUMONIA: A DIAGNOSIS IN THE EYE OF THE BEHOLDER

Apparently, when it comes to pneumonia, the diagnosis is in the eye of the beholder. Different physicians have different thresholds for applying the label. In the wake of quality efforts to ensure that emergency physicians deliver antibiotics within 4 hours, emergency doctors have been shown to have worse accuracy in diagnosing pneumonia.¹ But worse accuracy compared with what standard?

In an investigation by Welker et al,¹ the standard definition of pneumonia was based on the one favored by the US Food and Drug Administration for clinical trials. Patients had to have all of the following:

• A new or increasing infiltrate on radiography or CT
• A fever, an elevated white blood cell count, or a shift to immature polymorphonuclear leukocytes
• At least two signs or symptoms of the condition (eg, cough, dyspnea, egophany).

Although this definition is reasonable and ensures homogeneity in clinical trials, it is not steadfastly adhered to in clinical practice and has never been shown to cleanly delineate a population that benefits from antibiotics.

Another challenge to devising a perfect definition of pneumonia is the lack of a pathologic gold standard. Based on a review of 17,340 Medicare patients hospitalized for community-acquired pneumonia, microbial confirmation is often of little assistance, and a probable pathogen is identified in only 7.6% of cases.⁶

RATES OF OUTPATIENT DIAGNOSIS ARE LIKELY SIMILAR

Thus far, we have examined trends in inpatient diagnosis but not those of outpatient diagnosis. There is no well-done observational study that documents outpatient trends, but there is little reason to suppose the trends are different. Risk-scoring systems in pneumonia, such as the PORT⁷ and the CURB-65,⁸ have been designed to decrease unnecessary inpatient admissions, but they do not lend clarity to the diagnosis itself.

The central problem with pneumonia, as with many long-recognized clinical conditions, is that the diagnosis is separated from the treatment. In other words, although physicians are confident that antibiotics benefit patients who have what Sir William Osler would have called pneumonia (elevated white blood cell count, fever, cough, dyspnea, pleurisy, egophany, lobular infiltrate), we don’t know whether the treatment benefits patients whose pneumonia would have been unrecognizable decades ago (with cough, low-grade fever, and infiltrate on CT alone). Improvements in imaging may exacerbate the problem. In this sense, pneumonia exists on a spectrum, as do many medical diagnoses. Not all cases are equally severe, and some may not deserve to be labeled as pneumonia.

No randomized trial has compared antibiotics against supportive care in pneumonia, and, likely, no such trial is needed for clear cases. However, with the growing number of soft diagnoses, randomized trials are desperately needed to delineate where harms outweigh benefits, and where the fuzzy edge of the pneumonia diagnosis must end. And as is always the case with studies that challenge a standard of care, null results should prompt further trials.

WELL-DESIGNED TRIALS COULD END THE UNCERTAINTY

In the next few years, clinical trials, rationally planned, may end most of the uncertainty regarding pneumonia.

Existing observational data may be used to identify groups of patients who, in today’s world, are diagnosed with pneumonia but who do exceptionally well (eg, younger patients with fewer comorbidities, who present with low-grade fever but no signs of consolidation on physical examination, and with dubious results on chest radiography). These are patients for whom equipoise exists, and randomized trials should compare a strategy of antibiotics with a strategy of best supportive care. Trials should be powered for patient-centered outcomes, such as the duration and the complications of illness. The death rate should be scrupulously recorded.

Patients whose pneumonia would have been unrecognizable decades ago should be another target population for the trials I propose.

In a short time, pneumonia may become synonymous with a set of factors for lung infection that predict who will benefit from antibiotics, and who can be safely followed. Already, we are moving toward this standard in other diseases.⁹ For pulmonary embolism, ongoing trials are testing if anticoagulation can be safely omitted in patients with subsegmental clots (clinicaltrials.gov identifier NCT01455818). Such trials are, at last, translating old diagnoses into the language of evidence-based medicine.

For patients with pneumonia who are not hospitalized, the current outpatient therapy is based on data from studies that show a low rate of failure with empiric treatment based on consideration of the common pathogens for this condition, with few patients subsequently requiring hospitalization. Today, this reasoning is inadequate. The basis for any therapy must be proven benefit for patients with a defined condition compared with a lesser strategy. Data already demonstrate that a short course of antibiotics is no worse than a long course for many hospitalized and outpatients with pneumonia,^10,11 but many other patients may require no treatment at all. The time has come to find out.