木瓜直播

A 33-year-old Caucasian woman presents to a community hospital with fever and cough; she is very short of breath, and explains that her symptoms have worsened progressively over the past 24 hours. She says she is a smoker who returned to the habit about 8 months previously after several years of abstaining from tobacco. She notes that she is smoking the same amount as she had prior to quitting.

She has no history of significant respiratory illness aside from a mild upper respiratory infection several years before, which was successfully treated with oral antibiotics. More notably, she has had three previous transient ischemic attacks as a result of a methylenetetrahydrofolate reductase gene mutation. She is not taking any medications regularly.

The patient is employed as a customer service agent in a store. She is not aware of exposure to any sick contacts or hazardous environmental toxins that might explain her symptoms.

After she presents at the outside hospital, clinicians order a computed tomography (CT) scan of her chest. This reveals diffuse ground-glass opacities in all lobes, as well as small bilateral pleural effusions.

The patient is diagnosed with bacterial community-acquired pneumonia. For the next 48 hours, she receives oxygen by high-flow nasal cannula (HFNC) as well as vancomycin, ceftriaxone, and azithromycin.

Despite this treatment regimen, her fever persists, and she remains tachypneic and tachycardic. Clinicians also note that the patient becomes increasingly hypoxemic during minimal exertion, despite receiving high-flow oxygen. Given her deteriorating condition, the patient is transferred to a tertiary care center for pulmonary evaluation.

At the time of her admittance to the tertiary care hospital, her respiratory rate is approximately 35 bpm, and her heart rate is 130 bpm, in sinus rhythm.

Physical examination notes increased breathing effort and inspiratory crackles in all lung fields. Her white blood cell count is 14.2 k/mm³, with 90% neutrophils, 3.5% lymphocytes, 2.3% monocytes, and 3.2% eosinophils.

Arterial blood gas measured with the patient receiving 5 L of oxygen via nasal cannula reveals a pH of 7.43, a PCO2 of 39 mm Hg, pO2 of 68 mm Hg, and a bicarbonate of 26 mEq/L. Her procalcitonin level is 2.46 ng/mL (reference range <0.05 ng/mL). Chest radiograph showed diffuse infiltrates.

The results of tests performed at the community hospital -- including a respiratory viral polymerase chain reaction pathogen panel, urinary streptococcal and Legionella antigens, sputum culture, and blood cultures -- are all negative. Clinicians continue her antibiotic treatment and schedule a bronchoscopy the following morning.

60 Hours After Initial Presentation to Hospital

However, the patient's respiratory condition worsens steadily over the 10 hours following her admittance to the tertiary care center, despite her now being on HFNC at a fraction of inspired oxygen of 80% and a flow rate of 50 L/min. Before the bronchoscopy can be performed, growing concern for potential respiratory arrest leads clinicians to intubate the patient and start her on mechanical ventilation.This is followed immediately with bronchoscopy with bronchoalveolar lavage (BAL).

Testing of the BAL fluid reveals a white blood cell count of 738/mm³, with 45% eosinophils. Culture of bronchoalveolar lavage fluid does not produce any organisms.

Clinicians immediately discontinue treatment with antibiotics and initiate 125 mg of intravenous methylprednisolone every 12 hours. Following this change of treatment, the patient shows rapid improvement, such that 24 hours later she is extubated to supplemental oxygen by nasal cannula. Over the course of the next 24 hours, she is gradually weaned off supplemental oxygen completely.

About 72 hours after the initial tests showed a procalcitonin level of 2.46 ng/mL, her level has fallen to 0.45 ng/mL. The patient is transitioned to 60 mg of oral prednisone once daily, with a weekly 10 mg decrease in dose during the following several weeks.

Four days after admission to the tertiary hospital, the patient is discharged.

At follow-up clinic visit clinic 8 weeks later, she reports feeling back to normal, with no breathing difficulties or other persistent respiratory symptoms. A chest radiograph reveals resolution of infiltrates. She is advised of the importance of smoking cessation.

Discussion

Clinicians reporting this suggest its most notable feature is the elevated procalcitonin level observed in a patient who has acute eosinophilic pneumonia (AEP) rather than community-acquired pneumonia.

The levels of procalcitonin -- a protein expressed by the C cells in the thyroid gland and by neuroendocrine cells in the lungs and intestines -- are normally undetectable. Importantly in this case, procalcitonin is expressed in response to bacterial infections, while it is suppressed during viral infections.

As well, concentrations of procalcitonin fall rapidly during recovery from acute bacterial infections. This points to a potential adjunctive role for procalcitonin in diagnosing and managing patients with suspected systemic infections, and to help guide antibiotic prescribing practices.

Secretion of procalcitonin can occur for various reasons, depending on whether it is stimulated by the thyroid or other organs, the case authors note. Thyroid-related stimuli for C-cell expression of procalcitonin include hypercalcemia, glucagon, and gastrin. Non-thyroid mechanisms of procalcitonin expression include bacterial endotoxins, and inflammatory cytokines such as tumor necrosis factor, interleukin (IL)-1, IL-2, and IL-6.

The clinicians note that the mechanism behind this patient's elevated procalcitonin was not clear, and explained that there are five possible explanations for this that have been suggested in the literature:

• Higher levels of IL-2 have been noted in patients with AEP, compared with those seen in healthy volunteers and in patients with chronic eosinophilic pneumonia (CEP)

• T-helper 2 (Th2) cells, like many other immune cells, play a prominent part in AEP, and one of the cytokine triggers of Th2 cells is IL-2

• Indirect evidence suggests that IL-1 may also be elevated in the presence of AEP

• There are many known inflammatory conditions beyond LRTIs -- fungal infections, burns, trauma, pancreatitis, and all types of shock can cause elevated procalcitonin levels, supporting the hypothesis that AEP might also cause an elevation

• A link has been established between other eosinophilic conditions and elevations in procalcitonin levels

Procalcitonin: Distinguishing Bacterial From Viral LRTIs

Reports of patients with AEP have noted both normal and elevated procalcitonin levels, the case authors said, raising the possibility of differing pathophysiology between cases of AEP. Given that procalcitonin is elevated in bacterial LRTIs and suppressed in viral LRTIs, procalcitonin does have a potential role in bacterial LRTIs from viral LRTIs.

The authors cited a recent suggesting that its measurement in acute respiratory infections reduces antibiotic exposure, side effects, and improves survival. However, the authors urge caution in interpretation of test results, noting that many conditions can cause elevated procalcitonin.

About Eosinophilic Lung Disease

CEP is typically diagnosed by a triad of clinical symptoms including pulmonary symptoms, eosinophilia, and characteristic radiographic abnormalities. The case authors noted that despite their patient's female gender and her age (30-50) -- features associated with an increased risk of CEP -- her illness fulfilled all four criteria needed to make a diagnosis of AEP:

• Acute respiratory illness of less than a month's duration

• Pulmonary infiltrates on imaging

• More than 25% eosinophils in BAL fluid

• Absence of another specific pulmonary eosinophilic disease

The authors acknowledged the possibility that their patient's procalcitonin elevation might be due to an infectious process, and her clinical improvement could be related to her brief 2.5 days of antibiotic treatment. Nevertheless, she subsequently deteriorated to the point of requiring mechanical ventilation, and antibiotics were discontinued. Her rapid improvement after initiating treatment with corticosteroids is a hallmark of AEP.

As well, the case authors cited an influential paper suggesting that AEP can be distinguished from CEP by its rapid onset, greater severity, and increased likelihood of respiratory failure, all of which apply to this patient. Other features also consistent with AEP seen in this case include tobacco use, lack of atopic disease, diffuse infiltrates on imaging (rather than the predominantly peripheral infiltrates often seen in CEP, the so-called "photographic negative" of pulmonary edema), and the presence of bilateral pleural effusions, noted in an estimated 90% of patients with AEP.

Conclusion

As a rare condition that closely resembles other more common diseases, particularly bacterial pneumonia, AEP may be difficult for physicians to recognize, the case authors wrote, emphasizing that it is vital to realize that elevated procalcitonin levels do not rule out AEP. A prompt diagnosis is important, since treatment of AEP differs from that of bacterial pneumonia, and left untreated, patients may experience a precipitous decline or even death.

Assessment of procalcitonin in patients with AEP will help confirm whether the relationship is causal.

Comment