Epigenetic factors
Methamphetamine addiction is persistent for many individuals, with 61% of individuals treated for addiction relapsing within one year. About half of those with methamphetamine addiction continue with use over a ten-year period, while the other half reduce use starting at about one to four years after initial use.The frequent persistence of addiction suggests that long-lasting changes in gene expression may occur in particular regions of the brain, and may contribute importantly to the addiction phenotype. Recently a crucial role has been found for epigenetic mechanisms in driving lasting changes in gene expression in the brain.A review in 2015 summarized a number of studies involving chronic methamphetamine use in rodents. Epigenetic alterations were observed in the brain reward pathways, including areas like ventral tegmental area, nucleus accumbens, and dorsal striatum, the hippocampus, and the prefrontal cortex. Chronic methamphetamine use caused gene-specific histone acetylations, deacetylations and methylations. Gene-specific DNA methylations in particular regions of the brain were also observed. The various epigenetic alterations caused downregulations or upregulations of specific genes important in addiction. For instance, chronic methamphetamine use caused methylation of the lysine in position 4 of histone 3 located at the promoters of the c-fos and the C-C chemokine receptor 2 (ccr2) genes, activating those genes in the nucleus accumbens (NAc). c-fos is well known to be important in addiction. The ccr2 gene is also important in addiction, since mutational inactivation of this gene impairs addiction.In methamphetamine addicted rats, epigenetic regulation through reduced acetylation of histones, in brain striatal neurons, caused reduced transcription of glutamate receptors.
Computed tomography (CT) may be used to confirm the diagnosis. Often the findings are typical enough to allow the doctor to make a diagnosis without ordering additional tests. To confirm the diagnosis, a doctor may perform a lung biopsy using a bronchoscope. Many times, a larger specimen is needed and must be removed surgically. Plain chest radiography shows normal lung volumes, with characteristic patchy unilateral or bilateral consolidation. Small nodular opacities occur in up to 50% of patients and large nodules in 15%. On high resolution computed tomography, airspace consolidation with air bronchograms is present in more than 90% of patients, often with a lower zone predominance. A subpleural or peribronchiolar distribution is noted in up to 50% of patients. Ground glass appearance or hazy opacities associated with the consolidation are detected in most patients. Histologically, cryptogenic organizing pneumonia is characterized by the presence of polypoid plugs of loose organizing connective tissue (Masson bodies) within alveolar ducts, alveoli, and bronchioles. Unusual presentations of organizing pneumonia
While patchy bilateral disease is typical, there are unusual variants of organizing pneumonia where it may appear as multiple nodules or masses. One rare presentation, focal organizing pneumonia, may be indistinguishable from lung cancer based on imaging alone, requiring biopsy or surgical resection to make the diagnosis. Complications
Rare cases of COP have induced with lobar cicatricial atelectasis. Treatment
Systemic steroids are considered the first line treatment for organizing pneumonia, with patients often having clinical improvement within 72 hours of steroid initiation and most patients achieving recovery.