## 1 Introduction  
Vitamin D3, also known as cholecalciferol, next to vitamin D2 (ergocalciferol; characteristic for mushrooms and plants) is the major form of vitamin D. Vitamin D is synthesized in the skin from 7-dehydrocholesterol in response to UVB radiation (290-315 nm) and/or is absorbed in the diet in the form of vitamin D2 or vitamin D3. Both the ergocalciferol and cholecalciferol forms undergo the same two-step activation to 25(OH)-vitamin D3 (calcidiol), with the participation of 25-hydroxylases CYP2R1 and CYP2A1 (liver enzymes containing cytochrome P450), and further to biologically active 1,25(OH)2-vitamin D3 (calcitriol), with the participation of 1-hydroxylase CYP27B1--an enzyme found in the kidneys as well as extraran1 tissues [1]. Although there are two independent ways of obtaining vitamin D3 via the human body (endogenous synthesis and diet), its deficiency, defined as a serum concentration of 25(OH)-vitamin D below 50 nmol/L or 20 ng/mL [2], was recognized as a pandemic with serious health consequences including chronic respiratory diseases [3, 4, 5, 6, 7, 8, 9]. As revealed in scientific studies over the last two decades, vitamin D3 deficiency significantly elevated the risk of development and severity of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), lung cancer, idiopathic pulmonary fibrosis (IPF), and allergic inflammation as well as several respiratory infections including COVID-19 or tuberculosis [3, 4, 5]. At first sight, the easiest way to obtain the proper vitamin D3 content seems to be sun exposure, but the growing awareness of society about the pro-carcinogenic and pro-aging effects of UVB radiation on the skin [7, 10, 11], as well as a multitude of factors disruptingthe process of endogenous synthesis of vitamin D3 (e.g., altitude, latitude, season, time of day, skin pigmentation, age, use of sunscreen, and solar filters) [2; 4; 6; 7; 11; 12; 13], resulted in most strategies for neutralizing vitamin D3 deficiencies being based on vitamin D supplementation through the digestive route, including the prevention and treatment the pulmonary diseases [2; 3; 4; 7; 13]. Nevertheless, revision of the most important clinical studies focused on vitamin D3 role in several respiratory disorders, provided ambiguous results on the effectiveness of therapy based on supplementation with vitamin D metabolites, and revealed that achieving and maintaining the physiological level of calcitriol in pulmonary compartments requires more than just increasing this compound intake with food, supplements, or drugs. The main reason for the failure of this therapeutic strategy was the fact that the investigated patients suffered from other comorbidities as well as metabolic disorders disrupting the calcitriol synthesis [3; 4]. Furthermore, vitamin D supplementation is also burdened with the risk of vitamin D overdose, leading to hypercalcemia, hypercalciuria, or hyperphosphatemia, and in the case of their non-treatment to kidney stones, calcification of blood vessels, and organ parenchyma [7]. The increased risk of side effects after oral or parenteral administration of calcitriol or its direct precursor (calcidiol) is easy to understand when we realize that calcidiol to calcitriol transformation can occur not only in kidneys but also in many other sites [1; 14], either locally produced or directly delivered 1,25(OH)\({}_{2}\)-vitamin D3 after binding with vitamin D receptor (VDR), the presence of which has been proven in almost every nucleated cell in our body to regulate the expression over 200 different genes [1; 14; 15]. Thus, direct delivery of calcidiol and/or calcitriol to the respiratory system in order to prevent or treat pulmonary diseases associated with vitamin D3 deficiencies seems to be an obvious option to restore the physiological level of this hormone, as well as revealing its beneficial pro-health effect without unnecessary and uncontrolled activation of vitamin-D-target genes in other body compartments.