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Idiopathic Pulmonary Fibrosis

What is Idiopathic Pulmonary Fibrosis (IPF)?

Idiopathic pulmonary fibrosis (IPF) is the chronic and progressively worsening scarring (fibrosis) of lung tissue. The cause of this fibrosis is not known (idiopathic). The lung tissue stiffens, making it increasingly difficult for those with IPF to breathe. IPF is generally irreversible and eventually leads to fatal respiratory failure.

Unfortunately, there are currently no cure for IPF. Treatments are available that can slow the progression of the disease, and lung transplants may extend life expectancy. There are, however, many recent advances in our understanding of the disease and exploration of treatment options that give cause for optimism.

There are also emerging and natural integrative interventions like N-acetylcysteine, omega-3 fatty acids and senolytics such as quercetin, which are being explored for their anti-fibrotic and anti-inflammatory effects.

What Increases IPF Risk?

  • Genetic predisposition
  • Environmental exposure to factors such as cigarette smoke, metal or wood dust, and sand
  • Gastroesophageal reflux
  • Certain viral infections such as hepatitis C and human herpes virus-8
  • Age

What are the Signs and Symptoms of IPF?

  • Shortness of breath that worsens over time
  • Dry cough
  • Difficult or painful breathing
  • Fatigue
  • Weight loss
  • Anxiety and depression
  • “Crackling” sound in the lungs that can be heard with a stethoscope

What Treatments are Available for IPF?

  • Pulmonary rehabilitation, including exercise and education
  • Oral corticosteroids to inhibit cough
  • Psychological counseling after diagnosis
  • Antifibrotic agents such as pirfenidone and nintedanib
  • Lung transplant (uncommon for patients with IPF)

Note: Conventional treatments for IPF are generally palliative and aim to alleviate symptoms and possibly slow disease progression. Only lung transplants have been shown to increase survival time.

What Novel and Emerging IPF Therapies Appear Promising?

  • Mesenchymal stem cells to aid in repairing damaged lung tissue
  • Senolytics such as quercetin to help clear inflammatory senescent cells
  • Pentoxifylline, a drug generally used to improve vascular health, which has antifibrotic and anti-inflammatory activity
  • Antibodies against connective tissue growth factor to prevent fibrosis
  • Leukotriene antagonists to decrease inflammation
  • Lysophosphatidic acid (LPA) pathway inhibitors to prevent recruitment of fibroblasts
  • mTOR inhibitors such as rapamycin to decrease signaling in fibroblasts, as increased mTOR signaling may accelerate fibrosis
  • Proton pump inhibitors (PPIs) to treat accompanying gastroesophageal reflux. PPIs have also been associated with slower IPF progression
  • Metformin, an anti-diabetes drug, to decrease inflammation
  • Glucagon-like peptide-1, a signaling protein that can inhibit inflammation in pulmonary fibrosis

What Natural Interventions May Be Beneficial for IPF?

  • N-acetylcysteine (NAC). NAC has reduced oxidative stress and inflammation and prevented fibrosis in animal models of IFP. Genetic variations may play a part in the varying effectiveness of NAC to treat IPF in humans.
  • Niacin and taurine. The combination of niacin (vitamin B3) and taurine has been shown in preclinical research to inhibit the activities of pro-fibrotic inflammatory molecules.
  • Omega-3 fatty acids. Several animal studies have shown that omega-3 fatty acids could protect against experimentally induced IPF-like conditions.
  • Dehydroepiandrosterone (DHEA). DHEA, an endogenous androgen hormone, decreases with age and appears to be significantly lower in those with IPF. DHEA inhibited lung fibroblast proliferation in a laboratory setting as well.
  • Vitamin D. Chronic vitamin D deficiency in laboratory animals has been shown to promote fibrosis in lung tissue. Supplementation with vitamin D also decreased toxin-induced pulmonary fibrosis in mice.
  • Polyphenols. Certain plant compounds including curcumin,quercetin, resveratrol,epigallocatechin gallate (EGCG), and citrus flavonoids have demonstrated the ability to reduce fibrosis in animal models of IPF.
  • Phytochemicals. Other plant compounds including glycyrrhizic acid and ginsenoside Rg1 have shown promise in preventing or reversing pulmonary fibrosis in animal models of IPF.

Note: Most of the current research on natural interventions for IPF are animal or in vitro studies. However, based on the current understanding of IPF’s underlying mechanisms, these integrative therapies are of interest and may prove to be beneficial to those with IPF, although randomized controlled trials involving human subjects are urgently needed.

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