Coexistent Sarcoidosis and Tuberculosis: A Case Report.

Necrotizing granulomatous diseases of the lungs are usually dependent on a narrow range of differential diagnoses. Tuberculosis (TB) is responsible for the largest number of cases, while necrotizing sarcoidosis is generally considered a rare and easily distinguishable disease substantially based on histological features. However, this entity has become a viable diagnosis in the absence of mycobacteria isolation or when a remarkable clinical improvement cannot be achieved with the combination of anti-TB drugs at full dosage. The classic manifestations of TB and sarcoidosis have an overlapping range for which it is sometimes difficult to make a clinical diagnosis. Furthermore, the role of mycobacteria as a trigger antigen capable of evoking the clinical expression of sarcoidosis is a hypothesis supported by evidence from some cases. We report a case of bilateral tuberculous pleurisy in a 45-year-old male native of a North-African region with an atypical severe multisystem disease characterized by a fever resistant to anti-TB therapy and respondent to corticosteroid treatment. The choice to continue both steroid and anti-TB therapy proved to be correct for the late evidence of TB mycobacterial growth only on pleural specimens. The case described is suggestive of a coexistent systemic sarcoid manifestation and low-antigen TB, which is an underrecognized entity in the medical literature.

The Onset of Antinuclear Antibodies (ANAs) as a Potential Risk Factor for Mortality and Morbidity in COVID-19 Patients: A Single-Center Retrospective Study.

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) (p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.

Severe Asthma Network Italy Definition of Clinical Remission in Severe Asthma: A Delphi Consensus.

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry.

The Prescribing Practice for COPD: Relationship to Circadian Rhythm, Disease Severity, and Clinical Phenotype in the STORICO Observational Study.

INTRODUCTION: While selected clinical and laboratory findings are taken into account to find the best therapeutic strategies for chronic obstructive pulmonary disease (COPD), it is unknown whether the circadian rhythm of respiratory symptoms, a distinctive feature of COPD, affects the prescription pattern of pharmacological therapy. The main aim of this study was to verify whether the circadian rhythm of symptoms correlates with bronchodilating therapy prescribed to COPD patients as per clinical practice. A secondary objective was to assess the relationship between Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and circadian rhythm of symptoms and health status. METHODS: Five hundred sixty-six COPD patients were enrolled in the Italian multicenter STORICO study. Patients underwent a multidimensional assessment, and correlates of prescribed therapy were assessed through a multivariate multilevel model. RESULTS: As expected, patients in GOLD D stage were more likely to receive triple inhaled therapy than GOLD A-C patients, but the circadian rhythm of symptoms, assessed by the nighttime, morning, and daytime symptoms of the COPD questionnaire, was unrelated to the prescription pattern. The multivariate model showed that emphysematous (EM) patients had a 50% increased risk compared with patients affected by chronic bronchitis (CB) of being prescribed long-acting ß2-agonists (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) instead of triple therapy [relative risk (RR) EM versus CB 1.50, 95% CI 1.11, 2.03]. Symptoms, mainly in the early morning and daytime, were highly prevalent, even in GOLD B stage (76%). CONCLUSION: Even if we cannot infer about causality of the symptoms-therapy relationship, based on the structured recording of circadian symptoms clearly shows that symptoms are poorly controlled as the circadian rhythm of symptoms does not correlate with the prescription pattern, and many patients are symptomatic both at daytime and by nighttime. Thus, therapy should be better tailored to the individual needs, with special attention to control nocturnal symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03105999.

Adherence to omalizumab: A multicenter "real-world" study.

BACKGROUND: Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not been well studied in real-world settings. The aim of this study was to assess adherence to omalizumab and evaluate treatment effectiveness in relation to adherence. METHODS: This was a retrospective, observational, and multicenter real-world study. Omalizumab dose, timing of administration, and duration of treatment (<2 years; 2-4 years; > 4 years) were analyzed. Adherence was evaluated by examining rates of expected and missing doses. Good adherence (<10% of doses missed) and poor adherence (>10% doses missed) were determined. For effectiveness in relation to adherence of omalizumab we considered asthma exacerbations, hospitalizations, asthma control test (ACT), and Forced Expiratory Volume in 1 s (FEV1). RESULTS: A total of 196 patients were evaluated, and 161 were suitable for data analyses. Good adherence was shown in 90.7% of patients and poor adherence in 9.3%. Considering adherence in relation to treatment duration: <2 years, 87.8% of patients were adherent (expected doses, 1186; missed doses, 53); 2-4 years, 85.9% were adherent (expected doses, 2985; missed doses, 127); >4 years, 100% were adherent (expected doses, 6120; missed doses, none). Indices of efficacy between pre- and post-treatment showed significant improvement (p < 0.001). The effectiveness indices between pre- and post-treatment, among adherent and non-adherent patients, ACT, and asthma exacerbations both showed significant differences (p = 0.043 and p = 0.049, respectively). Binomial logistic regression analysis showed that increasing age, better ACT score, and 14-day timing were significantly associated with increased adherence to therapy. CONCLUSIONS: High adherence to omalizumab was demonstrated in a real-world setting, which was associated with better outcomes and control of asthma.

SARS-COV-2 Serological Profile in Healthcare Professionals of a Southern Italy Hospital.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the first coronavirus that has caused a pandemic. Assessing the prevalence of anti-SARS-CoV-2 in healthcare worker groups offers a unique opportunity to study the correlation between seroconversion and immunization because of their occupational exposure and a higher risk of contagion. The study enrolled 3242 asymptomatic employees of "Policlinico Riuniti", Foggia. After the first screening, we collected sequential serum samples for up to 23 weeks from the same subjects. In order to perform a longitudinal follow-up study and get information about the titration of IgG levels, we analyzed data from subjects (33) with at least two consecutive serological IgG-positive tests; 62 (1.9%; 95% CI: 1.4-2.3) tested positive for at least one anti-SARS-CoV-2 antibody. The seroprevalence was lower in the high-risk group 1.4% (6/428; 95% CI: 0.5-2.6) vs. the intermediate-risk group 2.0% (55/2736; 95% CI: 1.5-2.5). Overall, within eight weeks, we detected a mean reduction of -17% in IgG levels. Our data suggest a reduction of about 9.27 AU/mL every week (R2 = 0.35, p = 0.0003). This study revealed the prevalence of SARS-CoV-2 antibodies among Foggia's hospital healthcare staff (1.9%). Moreover, the IgG level reduction suggests that the serological response fades fast in asymptomatic infections.

Physical Activity as a New Tool to Evaluate the Response to Omalizumab and Mepolizumab in Severe Asthmatic Patients: A Pilot Study.

Asthma is a chronic inflammatory airway disease, representing one of the most severe pathologies in developed countries. Based on a report of the World Health Organization (WHO), it affects about 300 million people worldwide. Few studies have analyzed the effects of daily life physical activity (PA) levels in patients with asthma: moreover, little research has been carried out on PA levels in patients suffering from severe asthma (SA). This study aimed to investigate the PA levels in two groups of patients suffering from SA; in particular, this study analyzed the changes that occur in patients treated with biologic therapy (BT group) and patients who underwent traditional treatment (TT group) over 6 months. Moreover, this study represents a pilot study because, to the best of our knowledge, it is the first investigation that analyzed if the kind of biologic drug (omalizumab or mepolizumab) can produce differences in the PA levels of SA patients. Fifty SA patients were enrolled and PA parameters were monitored for 6 months. Subjects were divided into two treatment groups: TT (20 patients) and BT (30 patients), the BT group was further subdivided according to the drugs used (15, omalizumab; 15, mepolizumab). During drug treatment, all subjects improved their PA levels: indeed, considering the intragroup variation, the PA levels were significantly higher comparing the T6 levels to baseline (T0, p < 0.01). Considering the intragroup variation, it is very interesting to note that biologic therapy improved PA levels compared to the effects of traditional therapy; while at T0 there were no significant differences in the steps per day (SPD) values between the two groups (T0, p = 0.85), the differences become statistically significant at T1, T3, and T6 (T1, p = 0.019; T3, p = 3.48x10-6; T6, p = 4.78x10-10). As expected, the same differences were reported analyzing the energy expenditure data. In conclusion, this pilot study reports a positive relationship between biologic drug therapy and PA patterns, even if further studies are needed.

Values in Elderly People for Exhaled Nitric Oxide Study.

Ageing population is constantly increasing due to rising life expectancy; consequently, the percentage of the elderly patients with asthma is increasing, as well. Fractional exhaled nitric oxide (FeNO) is a biomarker of lung inflammation, and currently it is widely used in clinical practice for asthma diagnosis and monitoring. Yet, there are no data about normal values of FeNO in patients of more than 65 years of age with normal lung function. The aim of this study was to establish adult FeNO reference values for subjects older than 65 years, according to the international guidelines. FeNO was measured in 303 healthy, nonsmoking adults more than 65 years of age, with normal spirometry values measured using the online single-breath technique. The results were analyzed by chemiluminescent detection. The FeNO levels obtained range from 5.00 to 29.9 ppb, with a mean value of 12.48 ± 2.80 ppb. A significant association of FeNO levels with age (p < 0.05) was observed. There was no difference in FeNO values between men and women unlike what was observed in younger patients. FeNO levels in healthy controls over 65 years of age are influenced by age as in younger adults. However, there is no difference in FeNO values in male and female seniors, in contrast with what was found in younger adults in other studies. These data can be useful for the clinician to interpret the values of FeNO assessed during clinical practice.

Novelty in treatment of pulmonary fibrosis: pulmonary hypertension drugs and others.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown etiology with deteriorating respiratory function leading to respiratory failure. Corticosteroids, alone or in combination with immunosuppressive drugs such as azathioprine, colchicine, and cyclophosphamide, have been used with limited success. Interferon-gamma-1b showed a significant improvement in pulmonary function only in one study. Pirfenidone, cyclosporine and acetylcysteine may also be of benefit but data from studies are limited. Novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. Endothelin receptor antagonists have been shown to have possible beneficial effects in early stages of IPF. However, most recently, the so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended. We report a brief review on the present and possible future therapeutic options in IPF.