Why is Pet (cat/dog) allergen immunotherapy (ait) such a controversial topic? current perspectives and future directions.

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals."

COVID-19 lockdown, personal protective equipment, hyper-hygiene and allergy.

Summary: At the beginning of SARS-CoV 2 pandemic, in the absence of "targeted" therapies, the national health authorities have introduced some measures aimed at reducing the spread of infection in the community (lockdown, social distancing, personal protective equipment (PPE), personal hygiene and disinfection of living environments). All the containment measures have led to both positive and negative effects in patients with allergic diseases. We believe that further studies should be undertaken to investigate the possible correlations between SARS-CoV-2 infection and allergy, from a broader perspective. In particular, the risk factors for the development of undesirable effects should be investigated, especially in healthcare professionals forced to use PPE and sanitizing agents for a long time. However, since the COVID-19 pandemic probably will not be short-lived, the use of such protective aids will necessarily be widespread even in the general population. Therefore, further studies on the materials used for the production of PPE and sanitizing agents would be necessary to reduce their sensitizing and, in some cases, toxic potential.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Frequency of allergic sensitization to Can f 5 in North East Italy. An analysis of 1403 ISACs 112 (Component Resolved Diagnosis) collected retrospectively.

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5, a prostatic kallicrein expressed in the prostate and detectable only in male dogs. The aim of the present study was to establish the frequency, level of sensitization and association with other dog allergens of Can f 5, as assessed by Component Resolved Diagnosis (CRD- ISAC 112, ThermoFisher Scientific, Uppsala, Sweden), in North East Italy. A total of 1403 CRD ISAC 112 were examined retrospectively. Five-hundred twenty subjects (37 %) had a positive IgE response to at least one of the available animal allergens. Among these 520 subjects, 268 (51.5 %) showed at least one sensitization to dog allergens. Among dog-sensitized individuals, 183 (69.02%) showed IgE against Can f 5, and 106 (57.92%) were sensitized exclusively against Can f 5. The average Can f 5 specific IgE was 8.810 ISU-E, with 77.6 % of individuals showing medium or high values of specific IgE according to manufacturer's specifications. In conclusions, our data confirmed that there is a high number of sensitized patients to Can f 5, which have a high degree of allergic sensitization. These results should be taken into account by allergists managing dog allergic patients. In fact, clinical consequences of this sensitization regard respiratory allergy (burden of rhinitis/asthma), systemic reactions (anaphylaxis during sexual intercourse from cross-reaction with human prostatic antigen), allergen immunotherapy-AIT (likely ineffective in patients with exclusive sensitization), and preventive measures (possibility to own a female dog and a likely reduction of allergen passive transport). Further studies are needed to better explore these aspects in "real life".

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Dog allergy: can a prevalent or exclusive sensitization to Can f 5 be considered a lucky or negative event in real life?

Summary: Recent studies have shown the increasing relevance of allergic sensitization to Can f 5 (a prostatic kallikrein), which is an androgen-regulated protein expressed in the prostate and detectable only in male dogs. Can f 5 can be a prevalent or exclusive sensitizing agent in a considerable percentage of dog-allergic patients. Its specific allergenic characteristics are able to induce possible negative as well as positive clinical effects in individuals sensitized to dogs. In the present article we pointed out the possible pros or cons of sensitization to this allergen in real life. Further studies should be carried out to correctly assess some peculiar characteristics of Can f 5, in order to support the most of positive aspects and remedy at best the negative effects.

Letter to the Editor: Can dog allergen immunotherapy reduce concomitant allergic sensitization to other furry animals? A preliminary experience.

Summary: It has been shown that allergen immunotherapy (AIT) is effective in reducing symptoms of allergic asthma and rhinitis. Data on the efficacy are less convincing with regard to AIT for allergens of common pets (cats/dogs). We describe a case of dog allergy in which we explored if dog AIT (DAI) could reduce a concomitant allergic sensitization to other allergens of furry animals. Our case demonstrates the efficacy of sublingual DAI on SPTs, symptom score, and spirometric responses despite persistent exposure to dog allergens at home in a patient sensitized, but not exposed, to several other furry animals. Moreover, this is the first report suggesting that DAI is able to reduce SPTs responses not only to dog, but also to other furry animals such as rabbit, horse, mouse, rat, hamster, cow. We recommend an accurate anamnesis and diagnosis of dog allergy before prescribing DAI. In particular, the use of ImmunoCAP ISAC is essential to verify the presence of IgE to lipocalins / albumins belonging to other furry animals. Obviously further studies carried out by using different DAI schedules, allergen amount and time of re-evaluation, laboratory procedure should be performed to confirm our findings.

Thunderstorm-related asthma: what happens and why.

The fifth report issued by the Intergovernmental Panel on Climate Change forecasts that greenhouse gases will increase the global temperature as well as the frequency of extreme weather phenomena. An increasing body of evidence shows the occurrence of severe asthma epidemics during thunderstorms in the pollen season, in various geographical zones. The main hypotheses explaining association between thunderstorms and asthma claim that thunderstorms can concentrate pollen grains at ground level which may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients suffering from pollen allergies may inhale a high concentration of the allergenic material that is dispersed into the atmosphere, which in turn can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events.

Can the presence of cat/dog at home be considered the only criterion of exposure to cat/dog allergens? A likely underestimated bias in clinical practice and in large epidemiological studies.

An important aspect of allergic sensitization to furry animals is the association of dog and cat exposure in early childhood with the incidence of respective allergies later in life. This topic is very controversial, because some authors have found a "facilitating" effect, while others have noticed a "protective" or even no significant effect in individuals living in urban areas. It is likely that some biases could be responsible of these contradictory findings. Cat/dog ownership or their presence in indoor environments are considered usually the main criteria to assess the exposure to these pets in studies' questionnaires. Even in clinical practice "are there animals at home?" is the common query usually done when collecting anamnestic data. In our opinion, these commonly used questions should not be considered the main index of exposure to pet allergens, because they can lead to erroneous interpretation of the clinical significance of positive skin prick tests for pet allergens as well as of the real risk of exposure to allergens of dog/cat in epidemiological studies. Consequently, we suggest a new, more realistic, classification of modalities of exposure to pet allergens in "real life" based on five possible conditions.

Allergy in urban elderly population living in Campania region (Southern Italy). A multicenter study.

Given the increasing life expectancy observed in Western countries, there is a marked interest to know more about how aging could influence respiratory health. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic elders living in Campania region area (Southern Italy). Fourteen Allergy units or Centres examined a total of 462 patients. In this context 215 (46.53%) had positive skin prick tests (SPTs) to at least one allergen and were diagnosed with respiratory allergy. Parietaria represents the most common sensitizing agent in elders living in Campania region, followed by dust mites, grass pollen and Olea europaea. A relatively high percentage of atopic subjects suffered from respiratory symptoms at a fairly advanced age, namely 8.3% at 60-64 years, 10.2% at 65-70 and 5.7% at > 70 years. In conclusion, the prevalence and clinical significance of airway allergic sensitization in the elderly living in Campania region is more significant than expected in latter stages of life. Physicians should not neglect the role of atopy as a risk factor for the onset of allergic respiratory symptoms even in elderly patients.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.

Sensitization to cockroach allergens in the urban atopic populations living in Campania district (southern Italy). A multicenter study.

BACKGROUND: Although cockroach (CR) is an important cause of allergic sensitization worldwide, only a few data are available in Italy and in a previous study we have observed, in Naples area, a low prevalence of CR sensitization. OBJECTIVES: We sought to perform a prospective study for assessing the prevalence of allergic sensitization to CR in a sample of atopic population living in Campania district area (Southern Italy). METHODS: Ten Allergy Units or Centres of Campania district participated in this cross-sectional study. Each centre was required to collect the results of at least 100 allergy consultations in consecutive outpatients referred for actual or suspected respiratory allergy. We registered demographic data, type and duration of respiratory symptoms, pets ownership, possible exposure to CR allergens, results of the skin prick tests (SPTs). RESULTS: A total of 1477 patients were examined, 985 (66.68%) had a SPTs positivity to at least one allergen. In this context, ninety were sensitized to CR, thus the overall sensitization prevalence in subjects with respiratory allergy was 6.09% ranging between 0-11% and only five patients were mono-sensitized. Thirteen patients reported rhinitis (R) + bronchial asthma (A), twenty-one R + A + conjunctivitis (C), thirty-seven R + C, five only A and eleven individuals only R. Sixty-seven patients exhibited persistent and twenty-three intermittent symptoms. Dust mite constituted the first cause of associated sensitization to CR. CONCLUSIONS: The prevalence of allergic sensitization to CR is not negligible in population living in Campania district and shows a higher trend in comparison to that found recently and some years ago in Naples area. Finally, we suggest atopic individuals and especially those highly sensitized to mite allergens or those living in low-income areas to be tested by SPTs / evaluation of serum specific IgE to CR allergens to exclude the occurrence of CR allergic sensitization.

CDK9 inhibition as an effective therapy for small cell lung cancer.

Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC.