Interstitial And Fibrotic Lung Disease

1.

A 62-year-old man presents to your clinic for follow-up evaluation of shortness of breath and dry cough. His breathlessness on exertion started insidiously 6 months ago. Review of his evaluation reveals pulmonary function tests consistent with restriction and severely decreased diffusing capacity of the lung for carbon monoxide (DLCO). Highresolution computed tomography (HRCT) demonstrates bibasilar reticular abnormalities without ground-glass opacities or consolidation. A transbronchial lung biopsy was nondiagnostic. All serologies for connective tissue disease have been negative, and on repeat history today, the patient denies any past exposure to heavy metals, chemical toxins, molds, dusts, or asbestosis. On examination today, you note a resting O2 saturation of 88% on room air and bibasilar inspiratory crackles. There is no jugular venous distention, s3, or peripheral edema.

Which of the following is the most likely diagnosis for this patient?

Acute interstitial pneumonitis

Cryptogenic organizing pneumonia (COP)

Idiopathic pulmonary fibrosis (IPF)

Mycoplasma pneumonia

Congestive heart failure

Diagnosing IPF with certainty requires the fi nding of UIP on pathology in the appropriate clinical setting, namely, the exclusion of other causes of UIP, such as drug toxicities, exposures, and collagen vascular diseases. In the absence of a surgical biopsy, the American Thoracic Society/European Respiratory Society (ATS/ERS), in its consensus statement of 2000, outlined major and minor criteria in diagnosing IPF. In this schema, all major criteria and at least three of the four minor criteria should be present to make a confi -dent diagnosis of IPF in an immunocompetent host. The major criteria are exclusion of other known causes of diffuse parenchymal lung disease, abnormal pulmonary function with evidence of restriction and impaired gas exchange, bibasilar reticular abnormalities with minimal ground-glass opacities on HRCT, and transbronchial lung biopsy or bronchoalveolar lavage showing no features to support an alternative diagnosis. Minor criteria are age greater than 50 years, insidious onset of otherwise unexplaineddyspnea on exertion, duration of illness more than 3 months, and bibasilar, inspiratory crackles (dry or "Velcro"-like in quality).

Explanation

Diagnosing IPF with certainty requires the fi nding of UIP on pathology in the appropriate clinical setting, namely, the exclusion of other causes of UIP, such as drug toxicities, exposures, and collagen vascular diseases. In the absence of a surgical biopsy, the American Thoracic Society/European Respiratory Society (ATS/ERS), in its consensus statement of 2000, outlined major and minor criteria in diagnosing IPF. In this schema, all major criteria and at least three of the four minor criteria should be present to make a confi -dent diagnosis of IPF in an immunocompetent host. The major criteria are exclusion of other known causes of diffuse parenchymal lung disease, abnormal pulmonary function with evidence of restriction and impaired gas exchange, bibasilar reticular abnormalities with minimal ground-glass opacities on HRCT, and transbronchial lung biopsy or bronchoalveolar lavage showing no features to support an alternative diagnosis. Minor criteria are age greater than 50 years, insidious onset of otherwise unexplaineddyspnea on exertion, duration of illness more than 3 months, and bibasilar, inspiratory crackles (dry or "Velcro"-like in quality).

2.

A 61-year-old man with hypertension and hyperlipidemia returns to your clinic for follow-up on cough and shortness of breath. Over the past several months, he has had several bouts of "pneumonia," which have not responded to moxifloxacin or amoxicillin outpatient therapy. His chest x-rays have demonstrated persistent alveolar opacities throughout the illness. After several courses of antibiotics and months of shortness of breath and productive cough, you referred the patient to a cardiothoracic surgeon for video-assisted thoracoscopic lung biopsy. Today you received a pathology report stating that the biopsy was consistent with cryptogenic organizing pneumonia (COP).

What is the most appropriate next step for this patient?

Prescribe a 3-month course of doxycycline

Prescribe prednisone, 60 mg daily

Initiate mycophenolate mofetil

Observe the patient; follow up in 3 months

Unlike many of the idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) can often be treated effectively, at least initially. Corticosteroids are the mainstay of initial therapy, typically at moderate to high doses over several months to a year. No standardized consensus has been reached: some treat with once-daily doses of 1 mg/kg prednisone (60 mg/day) for 1 to 3 months, followed by 40 mg/day for 3 months and then tapering for a total duration of 1 year, whereas others have suggested shorter courses initially. Although shorter courses may be effective in certain individuals, relapses are common, often within 1 to 3 months of discontinuing or even tapering corticosteroids. Parenteral methylprednisoloneat doses of 500 to 1,000 mg/day ("pulse dosing") has been recommended for particularly rapidly progressing forms of COP, and cytotoxic therapy with cyclophosphamideand azathioprine has been used.

Explanation

Unlike many of the idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) can often be treated effectively, at least initially. Corticosteroids are the mainstay of initial therapy, typically at moderate to high doses over several months to a year. No standardized consensus has been reached: some treat with once-daily doses of 1 mg/kg prednisone (60 mg/day) for 1 to 3 months, followed by 40 mg/day for 3 months and then tapering for a total duration of 1 year, whereas others have suggested shorter courses initially. Although shorter courses may be effective in certain individuals, relapses are common, often within 1 to 3 months of discontinuing or even tapering corticosteroids. Parenteral methylprednisoloneat doses of 500 to 1,000 mg/day ("pulse dosing") has been recommended for particularly rapidly progressing forms of COP, and cytotoxic therapy with cyclophosphamideand azathioprine has been used.

3.

A 49-year-old previously healthy man presented to the emergency room (ER) with 3 weeks of progressive shortness of breath. He has noticed headaches, myalgias, malaise, sore throat, and a productive cough. His dyspnea has progressed to the point that he is now markedly short of breath at rest. He denied any recent exposures or inhalation. On arrival to the ER, his O2 saturation was 82% on room air, and he was in marked respiratory distress. He was intubated and transferred to the intensive care unit. A chest x-ray on admission demonstrated bilateral pulmonary opacities. His arterial oxygen tension (PaO2) was 115 mm Hg on 100% fraction of inspired oxygen (FiO2). Right heart catheterization demonstrated a pulmonary capillary wedge pressure of 13 cm H2O. All cultures, including bronchoalveolar lavage fl uid, were negative for bacterial, fungal, or viral pathogens. Transbronchial biopsy revealed diffuse alveolar damage. A rapid fl u test was negative.

Which of the following is the most likely diagnosis in this patient?

Acute interstitial pneumonia

Nonspecific interstitial pneumonia

Lupus pneumonitis

Miliary tuberculosis

Desquamative interstitial pneumonia

The onset of AIP is typically abrupt, with several days of a fl ulike illness with headaches, myalgias, malaise, sore throat, and productive cough. Exertional dyspnea ensues, often becoming severe. Patients typically present within 3 weeks of the onset of their symptoms appearing quite ill. Fever is present in half of patients at presentation, but all investigations for infectious etiologies are, by defi nition, negative. Examination may show evidence of widespread consolidation or diffuse crackles. Digital clubbing is typically absent in AIP, and its presence might suggest a diagnosis of acute exacerbation of (undiagnosed) IPF. Pulmonary function testing, when done, shows a restrictive pattern with gas exchange impairments, which are often severe. Hypoxemia is present, and patients commonly require mechanical ventilation. By clinical criteria, patients meet the defi nition of ARDS, namely, an acute onset, a PaO2 to FIO2 ratio of less than 200, diffuse bilateral opacities on chest imaging, and a pulmonary arterial occlusion pressure of less than 18.

Explanation

The onset of AIP is typically abrupt, with several days of a fl ulike illness with headaches, myalgias, malaise, sore throat, and productive cough. Exertional dyspnea ensues, often becoming severe. Patients typically present within 3 weeks of the onset of their symptoms appearing quite ill. Fever is present in half of patients at presentation, but all investigations for infectious etiologies are, by defi nition, negative. Examination may show evidence of widespread consolidation or diffuse crackles. Digital clubbing is typically absent in AIP, and its presence might suggest a diagnosis of acute exacerbation of (undiagnosed) IPF. Pulmonary function testing, when done, shows a restrictive pattern with gas exchange impairments, which are often severe. Hypoxemia is present, and patients commonly require mechanical ventilation. By clinical criteria, patients meet the defi nition of ARDS, namely, an acute onset, a PaO2 to FIO2 ratio of less than 200, diffuse bilateral opacities on chest imaging, and a pulmonary arterial occlusion pressure of less than 18.

4.

A 68-year-old woman with known IPF presents to your offi ce for follow-up. She states that her lung breathing trouble seems to be about the same, but she has felt a little weaker lately. Today on examination, her O2 saturation is 93% on 2 L O2 by nasal cannula. Her lung examination again reveals coarse, Velcro-like inspiratory crackles at both bases. She does not have elevated jugular venous pressure or peripheral edema, but you do note clubbing. Her pulmonologist has recently been treating her lung disease with prednisone and azathioprine, but the patient is not sure if this is helping. You order an arterial blood gas, chest x-ray, pulmonary function testing, and a 6-minute walk test.

Which of the following findings would be most predictive of further clinical deterioration of the patient's disease?

Decrease in forced vital capacity (FVC) by 12% from her previous study

Moderate increase in reticular opacities on chest x-ray

Carbon dioxide tension (PCO2) > 45 mm Hg on arterial blood gas

Decrease in distance walked in 6 minutes by 10 meters

Ostensibly, similar patients may behave quite differently over time, and our ability to distinguish this on initial assessment is relatively poor. Several authors have investigated the predictive power of trends in clinical progression to predict mortality. A number of studies have now pointed to a change in FVC, often set at 10%, as being clinically predictive of further disease progression. Other measures of disease progression, such as measures of oxygenation (A-a gradient, DLCO, amount of desaturation on a 6-minute walk test) and a decrease in 6-minute walk distance, may have prognostic signifi cance. Of all of these, a change in FVC of 10% may be the most reliable end point.

Explanation

Ostensibly, similar patients may behave quite differently over time, and our ability to distinguish this on initial assessment is relatively poor. Several authors have investigated the predictive power of trends in clinical progression to predict mortality. A number of studies have now pointed to a change in FVC, often set at 10%, as being clinically predictive of further disease progression. Other measures of disease progression, such as measures of oxygenation (A-a gradient, DLCO, amount of desaturation on a 6-minute walk test) and a decrease in 6-minute walk distance, may have prognostic signifi cance. Of all of these, a change in FVC of 10% may be the most reliable end point.

5.

A 58-year-old male former smoker returns to your clinic for a follow-up appointment for IPF. On your initial evaluation, he reported several months of insidiously worsening shortness of breath and dry cough. He denied any significant previous exposures, and all serologies for connective tissue diseases were negative. HRCT demonstrated peripheral interstitial opacities with honeycombing and traction bronchiectasis. A surgical lung biopsy was consistent with usual interstitial pneumonia (UIP).

For this patient, which of the following therapies has proven survival benefit?

Prednisone

Prednisone + cyclophosphamide

Methotrexate

Lung transplantation

Colchicine

Unfortunately, there is no proven therapy for the treatment of IPF. In spite of these limitations, pulmonologists and internists continue to prescribe medications without proven benefi t in the hope that an individual patient might respond. Fortunately, more placebo-controlled trials are in progress or planned for the near future. Lung transplantation remains the only therapy for IPF with proven survival benefi t. Under the previous organ allocation system used in the United States for lung transplantation, time on the waiting list was paramount in a patient being offered a transplant. Under this system, the median time on the waiting list was roughly 2 years. As of May 2006, the allocation system was revised such that a complex, iterative formula comparing anticipated benefi t from transplantation with anticipated clinical course in the absence of transplantation now determines the priority of organ allocation. As a result, the waiting time for patients with IPF has decreased considerably.

Explanation

Unfortunately, there is no proven therapy for the treatment of IPF. In spite of these limitations, pulmonologists and internists continue to prescribe medications without proven benefi t in the hope that an individual patient might respond. Fortunately, more placebo-controlled trials are in progress or planned for the near future. Lung transplantation remains the only therapy for IPF with proven survival benefi t. Under the previous organ allocation system used in the United States for lung transplantation, time on the waiting list was paramount in a patient being offered a transplant. Under this system, the median time on the waiting list was roughly 2 years. As of May 2006, the allocation system was revised such that a complex, iterative formula comparing anticipated benefi t from transplantation with anticipated clinical course in the absence of transplantation now determines the priority of organ allocation. As a result, the waiting time for patients with IPF has decreased considerably.