Friday, January 15, 2010

Pulmonary Alveolar Proteinosis (PAP) vs Idiopathic Pulmonary Fibrosis (IPF) - Diagnostic Considerations
PAP is a rare clinical syndrome that is characterized by the accumulation of surfactant in the pulmonary airspaces (Greenhill SR and Kotton DN, 2009). Lung biopsies usually reveal presence of diastase-resistant intra-alveolar exudate with minimal interstitial fibrosis and "honeycombing". In some patients with PAP, however, interstitial fibrosis can be considerable and at least two PAP patients were initially thought to have IPF (Arbiser ZK et al., 2003). PAP is no longer idiopathic, since functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF) appears to cause the disease. The presence of autoantibodies against GM-CSF in serum is considered to be diagnostic for PAP (Kitamura T et al., 1999; Bonfield, TL et al., 2002). It is highly important to excude PAP as a possible diagnosis since the prognosis of PAP and IPF are different. The life expectancy of PAP patients is longer, 5-year mortality is 20% vs 80% for IPF patients. Also, patients with PAP favorably respond to pulmonary lavage and can possibly be treated with GM-CSF. It is unfortunate that GM-CSF antibodies test is not yet widely available in clinical laboratories.
Arbiser ZK et al. Ann Diagn Pathol 7:82-86, 2003
Bonfield TL et al. Clin Immunol 105:324-350, 2002.
Greenhill SR and Kotton. Chest 136:571-577, 2009
Kitamura T et al. J Exp Med 190:875-880, 1999.

Monday, January 4, 2010

IPF symptomatology

The first symptom of my disease, idiopathic pulmonary fibrosis (IPF), was cough. It appeared to be caused by a post-nasal drip. I assumed that my sinuses may have been infected and I contacted otolaryngologist who ordered scan of the sinuses and found nothing. The cough was initially non-productive, it lasted for ca 30 minutes every morning and subsided after breakfast. IPF was diagnosed at Yale pulmonary clinic on the basis of X-ray, pulmonary function tests and lung scan. It was explained to me that IPF is a terminal disease and that there are no FDA approved drugs for the treatment of IPF. The only therapy, recommended by the Thoracic society, consists of steroids (e.g. prednisolone) and/or immunosuppressants (e.g. azathioprine). This therapy has not been shown to prolong life expectancy, is ineffective in the majority of patients and is associated with substantial side effects. I chose not to be treated and used candies to reduce the severity of cough. I learned from the literature that antioxidants may have antifibrotic activity and treated myself with vitamin C (slow release), 1 g per day and N-acetyl cysteine ( 2 x 600 mg per day). The only other symptom I experienced early in the disease was what I called, "miniapnea", inability to breathe for a few seconds, followed by complete recovery. Thereafter, dyspnea during and after exertion became the major symptom.
Initially it was uphill walking that caused dyspnea, but gradually walking on the flat surface became difficult as well. Dyspnea was associated with oxygen desaturation, as measured with oximeter. Climbing steps to the 2nd floor at home reduced blood oxygen saturation very rapidly from 95% to 85 and eventually even to 78%. Breathing oxygen at 2 L/min for 5 to 10 minutes normalized oxygen levels. Desaturation below 90% was associated with dyspnea, dizziness, anxiety and occasional chest pain. The symptoms were proportional to the decrease in blood oxygen, they rapidly disappeared after oxygen inhalation. Thermoregulation appeared to be affected as well. Exposure of the skin to cold temperature led to oxygen desaturation and cough.
Another symptom was "burning feet" at night that was independent of actual skin or room temperature. The sensation was the same when the feet were hot or cold. Still another symptom was "running nose", nasal discharge of a very thin fluid, that was more pronounced during and after administration of oxygen.
Domestic tasks became difficult, I routinely desaturated in shower and switched to bath every second day. Initially, I could exercise on treadmill while inhaling oxygen, but later oxygen inhalation even at 3 L/min did not protect from desaturation during exercise. The disease appeared to progress in steps. The steps were initiated by common cold or other stress. Annual lung function tests indicated gradual decrease in vital capacity. I found it more and more difficult to maintain blood oxygen levels above 90%. According to the literature only 20% of patients are expecxted to survive 5 years after diagnosis. I am already in my 8th year. Does this mean that diagnosis may have been incorrect?