Supplementary Management with Pycnogenol(r)-Centellicum ® may Slow Down the Progression of Pulmonary Fibrosis and Improve Post-Covid-19 Lung Healing

may Slow Down the Progression of Pulmonary Fibrosis and Improve Post-Covid-19 Lung Healing. Biomed


Introduction
Idiopathic pulmonary fibrosis (IPF) is the most common issue of Idiopathic Interstitial Pneumonia(IIP) and causes progressive pulmonary fibrosis. Symptoms (exertional dyspnea, non-productive cough, and 'Velcro' lung crackles) tend to increase progressively.
The diagnosis of IPF is based on the clinical picture and High-Resolution CT Scans (HRCT) or lung biopsy, when needed. Currently, treatment with antifibrotic drugs and oxygen therapy may help relieving symptoms but it is not clear if the progression can be changed. Most patients show a progressive degeneration of the lungs with a median survival (possibly, based on initial conditions, management, and age) from 3 to 5 years [1][2][3][4][5]. Histology shows interstitial pneumonia in most cases. Environmental, genetic, and unknown factors contribute to alveolar epithelial cells dysfunction or reprogramming leading to the abnormal fibroproliferation in the lungs. The key histological findings (subpleural fibrosis with fibroblast foci, sites of dense proliferation and intense scarring), alternating with areas of apparently normal tissue are visible with a diffuse heterogeneity of the tissues. Scattered areas of interstitial inflammation (with lymphocytes and plasma cells) tend to increase in time. Accessory symptoms (low-grade fever or myalgias) are uncommon. Clubbing can be seen in some 50% of the cases.
A classic sign is the presence of fine dry inspiratory crackles (Velcro) at both bases of the lungs. Most blood tests tend to be normal. More severe signs (pulmonary hypertension and right ventricular dysfunction) may develop [1][2][3][4][5][6][7]. IPF is often overlooked or confused with bronchitis, asthma, or heart failure. Diagnosis is made with High-Resolution Computer Tomography (HRCT). Chest x-ray shows diffuse reticular opacities in the lower-peripheral zones, small cystic lesions (caused by honeycombing), and some dilated airway (traction bronchiectasis). HRCT shows diffuse, patchy, subpleural, reticular opacities in the lower and peripheral lung zones. Ground-glass opacities (in more than 30% of the lungs) tend to suggest a different diagnosis. Lab tests are basically within normal values in most patients. Lung's health of most subjects tends to deteriorate in a relatively short period of time.
The worst prognosis is related to older age, male sex, lower forced vital capacity and lower diffusing capacity of the lung for carbon monoxide or CO (D LCO also known as T LCO ). D LCO is the extent to which oxygen passes from the air sacs of the lungs into the bloodstream.
This refers to the test commonly used to evaluate this parameter.
Acute problems (infections, embolism, pneumothorax, and heart failure) may cause acute lung deterioration. This condition has a high mortality and morbidity: lung cancer is more frequent in these patients for concomitant risks, but the causes of death are associated with respiratory failure [6,7]. The aim of this study was  In these subjects, fibrosis of the lung was a 'secondary' problem and the effects on the lungs were studied as a corollary evaluation to the initial management of atherosclerosis. The main target was the evaluation of changes in the Karnofsky performance scale. Cardiac Ultrasound showed no signs of significant pulmonary hypertension.

Part I Idiopathic Interstitial Pneumonia
There was a good left ventricular function. There were no valvular abnormalities.
severe consequences. Pycnogenol ® and Centellicum ® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.   The 'slices' [4] are scanned for fibrotic components and for vascularization. The content of white 'speckles' corresponds to the presence of fibrotic elements. In a normal lung section of this type, the white components are about 8% of the section or less. Figure   2 shows an elaboration of a 'slice' of lung tissue with its 'white' components corresponding to high collagen level (full black is the density of blood). The same software is used to image the arterial plaques to define their content in fibrotic (white) components or i.e., thrombotic (black on ultrasound scans, same density of blood).
The role of the combination Pycnogenol®-Centellicum® to control fibrosis has been previously defined in several clinical models [10]. 150 mg/day of Pycnogenol® was administered in 3 doses and Centellicum® (centella asiatica) was given at the doses of 225 mg 3 times per day. Both supplements are produced by Horphag Research.
Statistics [11][12][13]. A number of at least 15 subjects for each group (SM and SM + supplementation) was considered necessary to evaluate differences in target parameters over 4 weeks. All results and data were considered as non-parametric; the Mann-Whitney U-test and the ANOVA were used for symptoms/complaints. A predictive analysis [14] was performed at the end of the study based on the observed data and results.

Part II: Post-COVID-19 Lung Disease
In an additional evaluation, subjects with Post-COVID-19 Lungs Disease (PCL), a second group of subjects (the study is in progress) were included in a registry; these were previously symptomatic patients, briefly admitted into hospitals (no ICU) and then sent home with some signs/symptoms (under control) with a standard management, based on the controls of the most common symptoms. A number of these subjects (all males) had also used as a supplementary management the combination of Pycnogenol® (150 mg/day in 3 doses) and Centellicum® (Centella asiatica, at the doses of 225 mg 3 times/daily). They were all using the supplementation before being diagnosed with COVID-19 and hospital admission, to slow down the progression of atherosclerotic, carotid plaques.

Standard management was based on anti-inflammatory drugs;
aerosols (no routine corticosteroids); antibiotics if indicated; vitamins, electrolytes, mild respiratory exercise (Triflo); appropriate diet (including proteins). Other drugs, like corticosteroids or cough meds, were used as needed. Table 3 shows the most common symptoms and the Karnofksy performance scale index in 2 weeks of observation or supplementation.

Part I. Idiopathic Interstitial Pneumonia
19 subjects with Idiopathic Interstitial Pneumonia were included in the study. 10 were treated with the Pycnogenol® Centellicum® combination and 9 served as controls. No side effects were seen for the supplementation. A good tolerability was observed. Table 2   and may suggest other diseases [15].Therapy is complex and

Part II. The Post-Covid-19 Lung (PCL) Experience
Preliminary results (Table 3) 18 subjects with post-COVID-19 lung disease were included in the study. 10 were treated with the Pycnogenol® Centellicum® combination and 8 served as controls.
Supplementation did not cause side effects and was well tolerated.
The preliminary results on symptoms associated withpost-COVID-19 Lung disease after 2 weeks were significantly improved with the supplement combination as compared with baseline.
Oxidative stress and the Karnofsky performance scale were significantly improved in the supplements group as compared with controls (p<0.05). Morphological CT or ultrasound scans will show (the study is in progress) the evolution of the tissue scarring, but over a longer period of time.

Conclusion
According to these observations, Pycnogenol® helps to control and decrease edema in several conditions and Centellicum® (Centella asiatica)-modulating the apposition of collagen in the affected tissues-possibly, slows down or modulates the development of irregular cicatrization, keloidal scarring and fibrosis [9][10]15]. More time and specific evaluation methods [16] are needed to evaluate this effect and a larger number of PCL patients may be considered for a disease that has affected almost 5 million subjects worldwide so far, leaving severe consequences.
Pycnogenol® and Centellicum® may improve the residual clinical picture in PCL and, in the long-term reduce the number of subjects progressing to lung fibrosis [8,16]. The key passage and evolution from edema to fibrosis seems to be slower or attenuated with this safe supplement combination both in IPF and in PCL.