Main Research Findings

Chronic respiratory diseases are the third leading cause of death worldwide, affecting approximately 550 million people. Asthma and chronic obstructive pulmonary disease (COPD) are the most common chronic respiratory diseases, with COPD being the leading cause of death. Despite differences in etiology and symptoms, a common feature of asthma and COPD is an underlying degree of airways inflammation. The nature and severity of this inflammation might differ between and within different respiratory conditions and pharmacological anti-inflammatory treatments are unlikely to be effective in all patients. A precision medicine approach is needed to selectively target patients to increase the chance of therapeutic success. 5

Inhibitors of the phosphodiesterase 4 (PDE4) enzyme like the oral PDE4 inhibitor roflumilast have shown a potential to reduce inflammatory-mediated processes and the frequency of exacerbations in certain groups of COPD patients with a chronic bronchitis phenotype. However, roflumilast use is dampened by class related side effects as nausea, diarrhea, weight loss and abdominal pain, resulting in both substantial treatment discontinuation in clinical practice and withdrawal from clinical trials. This has prompted the search for PDE4 inhibitors to be given by inhalation to reduce the systemic exposure (and thus optimize the systemic safety) and maximize the therapeutic effect in the lung. 5

Tanimilast (international non-proprietary name of CHF6001) is a novel highly potent and selective inhaled PDE4 inhibitor with proven anti-inflammatory properties in various inflammatory cells, including leukocytes derived from asthma and COPD patients, as well as in experimental rodent models of pulmonary inflammation. Inhaled tanimilast has reached phase III clinical development by showing promising pharmacodynamic results associated with a good tolerability and safety profile, with no evidence of PDE4 inhibitors class-related side effects. 5

Reasons for Side Effects

Side effects of PDE4 inhibitors are caused by their systemic effects, which are due to the fact that PDE4 is expressed in a variety of tissues and cells. 5

Common Side Effects

Nausea

Roflumilast has been associated with nausea as a side effect. However, inhaled tanimilast has shown no evidence of PDE4 inhibitor class-related side effects. 5

Diarrhea

Roflumilast has been associated with diarrhea as a side effect. However, inhaled tanimilast has shown no evidence of PDE4 inhibitor class-related side effects. 5

Weight Loss

Roflumilast has been associated with weight loss as a side effect. However, inhaled tanimilast has shown no evidence of PDE4 inhibitor class-related side effects. 5

Abdominal Pain

Roflumilast has been associated with abdominal pain as a side effect. However, inhaled tanimilast has shown no evidence of PDE4 inhibitor class-related side effects. 5

Side Effect Management

Nausea

Nausea can be managed through dietary changes and medications. For example, eating small, frequent meals, avoiding fatty foods, taking medications before meals, etc. 5

Diarrhea

Diarrhea can be managed through dietary changes and medications. For example, drinking plenty of fluids, avoiding foods high in fiber, taking antidiarrheal medications, etc. 5

Weight Loss

Weight loss can be managed through dietary changes and exercise. For example, eating a high-calorie diet, increasing exercise, etc. 5

Abdominal Pain

Abdominal pain can be managed through dietary changes and medications. For example, eating bland foods, taking pain relievers, etc. 5

Comparison Between Studies

Commonalities Between Studies

These studies suggest that PDE4 inhibitors may be effective for treating respiratory diseases. However, these studies are still in their early stages, and more research is needed to understand the safety and efficacy of PDE4 inhibitors. 5

Differences Between Studies

These studies differ in terms of the method of administration of PDE4 inhibitors, the target diseases, and the assessment criteria. Therefore, the results of these studies cannot be directly compared. 5

Real-Life Application Notes

PDE4 inhibitors may be effective for treating respiratory diseases, but it is important to consider the risk of side effects. If you are considering using a PDE4 inhibitor, follow your doctor's instructions and talk to them immediately if you experience any side effects. 5

Current Research Limitations

PDE4 inhibitor research is still in its early stages, and more research is needed to understand their safety and efficacy. Long-term safety and efficacy, in particular, have not yet been fully elucidated. 5

Future Research Directions

Further clinical trials are needed to better understand the safety and efficacy of PDE4 inhibitors. In particular, research is needed on long-term safety and efficacy, effects in different patient populations, the combined effects of PDE4 inhibitors and other treatments, etc. 5

Conclusion

PDE4 inhibitors are a new treatment that may be effective for treating respiratory diseases. However, PDE4 inhibitors are also associated with the risk of side effects. If you are considering using a PDE4 inhibitor, follow your doctor's instructions and talk to them immediately if you experience any side effects. 5