Penicillium genus is one of the most important fungal allergenic sources, associated mainly with upper and lower respiratory allergy including asthma, AR, allergic fungal sinusitis, and allergic broncho-pulmonary mycosis. It is also responsible for opportunistic infections, onychomycosis, keratomycosis, and non-allergic, non-invasive, fungal sinusitis (1, 33). Beside sensitization, allergy and opportunistic infections, Penicillium spp. release volatile organic compounds (VOCs) and mycotoxins, which can pose health threats through inhalation or ingestion, e.g., ingested mycotoxins from fermented cheese (37). VOCs are responsible of the moldy odor, which can be perceived in presence of growing Penicillium (38). Data on exposure to Penicillium spp., especially in indoor environments, are best interpreted in the context of multiple microbial communities. Indeed, fungal and microbial load and diversity may mitigate immune responses, especially during early life (39).
Allergic rhinitis
Penicillium spp. are reported to induce AR (18).
A study by Kołodziejczyk et al. (2016) addressed the clinical presentation and natural course of AR in outpatients from Poland. Patients (n= 229) sensitized only to molds were compared to patient’s mono- or polysensitized to other airborne allergens. Among the 239 mold-allergic patients, only 14 (5.9%) were sensitized (SPT or specific IgE) to P. chrysogenum, a far lower prevalence than A. fumigatus or Cladosporium herbarum. The study concluded that in mold allergic patients AR is milder, but with significant predisposition for bronchial asthma (40).
Asthma
Exposure to Penicillium spp. is a risk factor for asthma at all stages of its natural history inluding development, persistence, and severity, both in adults and in children (3, 41)
A prospective birth cohort study was conducted with 880 infants at high risk for developing asthma (defined as at least one older sibling with physician-diagnosed asthma) from Connecticut and western Massachusetts, USA. In this study, higher indoor concentrations of Penicillium spp. were linked with an increased rate of wheeze [RR =2.46; 95% Confidence Interval (CI) 1.63-3.70] and persistent cough (RR= 1.84; 95% CI 1.22-2.80) during the first year of life, after adjustment for potential confounding factors such as seasonal and housing characteristics, maternal asthma, and socio-economic status (2, 8). The same research group confirmed these findings in a cohort of 1233 asthmatic children (age 5-10 years): exposure and sensitization to any indoor airborne Penicillium species conveyed a higher risk of wheeze [Odds ratio (OR) 2.12, 95% CI 1.12-4.04], persistent cough (OR 2.01, 96% CI 1.05-3.85), and elevated asthma severity score (OR 1.99, 95% CI 1.06-3.72) in comparison to those who were not sensitized or exposed to Penicillium species (42).
The association between indoor mold growth and wheezing episodes in children was also found in a Finnish pediatric cohort study (3). In adult asthmatic patients, multiple reports found that Penicillium sensitization was associated with poor asthma control or higher severity score for asthma (20, 43). According to a cross sectional study by Woolnough et al. (2017) a significant correlation was observed between IgE sensitization to filamentous fungi and lung damage in asthma patients (44).
Similarly, a meta-analysis of 33 epidemiologic studies observed that adverse respiratory outcomes were increased by 30-50% in houses with damp indoor environment and mold growth (45). Current researches from the US, Europe, and World Health Organization (WHO) indicated damp indoor environment to be an important factor in inducing asthma (3).
At the pathophysiological level, Penicillium allergens exert both IgE-dependent and IgE-independent actions with synergistic effects. The alkaline serine proteases of Penicillium group 13 allergens (e.g., Pen ch 13) disrupt interepithelial tight junctions through direct action on occludin and induce bronchial epithelial cells to release proinflammatory cytokines (46, 47). IgE-mediated effects include histamine degranulation, which can be demonstrated in vitro through basophil activation triggered by Pen ch 13 (47).
Atopic Dermatitis
P. chrysogenum was commonly found in homes from Canada, which may be responsible for upper or lower respiratory tract infection and also skin reactions in allergic individuals (21). Among patients from Taiwan (n= 133, 1-67 years) with fungal sensitization, Penicillium sensitization was found in 74.6 % (44/59) patients with isolated AD and in 71% (22/31) of those diagnosed with both AD and respiratory disease (asthma or AR), at higher levels than in patients with isolated asthma or AR (41%, 18/43) (48).
Other diseases
A study evaluating fungi in sick building syndrome among 48 schools in the US found Penicillium spp. in 5.2% of samples, with P. chrysogenum as the predominant species (49).
Penicillium spp. has been linked to the development of hypersensitivity pneumonitis, often in the context of occupational allergies in highly diverse fields: wind instrument players, food industry workers, foresters, mushroom producers (50, 51).
Other topics
Penicillium spp. are also reported to produce several mycotoxins such as ochratoxin, citrinin, cyclopiazonic acid, mycophenolic acid, rubratoxin B, and patulin. These mycotoxins, especially ochratoxin and citrinin, can cause acute lesions and further can develop into cancer (52). P. chrysogenum is reported to cause black esophagus, endophthalmitis, and keratitis (35).