An unusual presentation of pulmonary lymphoma: When diffuse ground glass opacities can mean anything

Primary lung lymphoma (PLL) is a rare type of lymphoma confined to the lung at the time of diagnosis. Pulmonary diffuse large B cells lymphoma (P-DLBCL) is the second most common type of PLL and it usually appears radiologically as solitary or multiple nodules or areas of consolidation. We present the case of a 63-year-old Caucasian male who developed severe acute respiratory failure and diffuse ground glass opacities (GGO) on chest computerized tomography. Diffuse GGO may be the radiological expression of very different diseases, ranging from infectious processes to interstitial lung diseases (ILDs) and neoplastic diseases. In our case, pneumonia and de novo ILD were initially considered given the symptoms and past medical history. However, bronchoscopy with trans-bronchial biopsies demonstrated the presence of P-DLBCL, despite an unusual radiological presentation and negative cytological analyses on bronchoalveolar lavage. In conclusion, P-DLBCL should be considered among the many differential diagnoses of diffuse GGO

Positive end expiratory pressure in acute hypoxemic respiratory failure due to community acquired pneumonia: Do we need a personalized approach?

Background. Acute respiratory failure (ARF) is a life-threatening complication in patients with community acquired pneumonia (CAP). The use of non-invasive ventilation is controversial. With this prospective, observational study we aimed to describe a protocol to assess whether a patient with moderate-to-severe hypoxemic ARF secondary to CAP benefits, in clinical and laboratoristic terms, from the application of a positive end expiratory pressure (PEEP) + oxygen vs oxygen alone. Methods. Patients who benefit from PEEP application (PEEP-responders) were defined as those with partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increase > 20% and/or reduction of respiratory distress during PEEP + oxygen therapy compared to oxygen therapy alone. Clinical characteristics and outcomes were compared between PEEP-responders and PEEP-non responders. Results. Out of 41 patients, 27 (66%) benefit from PEEP application (PEEPresponders), the best response was obtained with a PEEP of 10 cmH2O in 13 patients, 7.5 cmH2O in eight and 5 cmH2O in six. PEEP-responders were less likely to present comorbidities compared to PEEP-non responders. No differences between groups were found in regards to endotracheal intubation criteria fullfillment, intensive care unit admission and in-hospital mortality, while PEEP-responders had a shorter length of hospital stay. Discussion. The application of a protocol to evaluate PEEP responsiveness might be useful in patients with moderate-to-severe hypoxemic ARF due to CAP in order to personalize and maximize the effectiveness of therapy, and prevent the inappropriate PEEP use. PEEP responsiveness does not seem to be associated with better outcomes, with the exception of a shorter length of hospital stay

Characterizing non-tuberculous mycobacteria infection in bronchiectasis

Chronic airway infection is a key aspect of the pathogenesis of bronchiectasis. A growing interest has been raised on non-tuberculous mycobacteria (NTM) infection. We aimed at describing the clinical characteristics, diagnostic process, therapeutic options and outcomes of bronchiectasis patients with pulmonary NTM (pNTM) disease. This was a prospective, observational study enrolling 261 adult bronchiectasis patients during the stable state at the San Gerardo Hospital, Monza, Italy, from 2012 to 2015. Three groups were identified: pNTM disease; chronic P. aeruginosa infection; chronic infection due to bacteria other than P. aeruginosa. NTM were isolated in 32 (12%) patients, and among them, a diagnosis of pNTM disease was reached in 23 cases. When compared to chronic P. aeruginosa infection, patients with pNTM were more likely to have cylindrical bronchiectasis and a “tree-in-bud” pattern, a history of weight loss, a lower disease severity and a lower number of pulmonary exacerbations. Among pNTM patients who started treatment, 68% showed a radiological improvement, and 37% achieved culture conversion without recurrence, while 21% showed NTM isolation recurrence. NTM isolation seems to be a frequent event in bronchiectasis patients, and few parameters might help to suspect NTM infection. Treatment indications and monitoring still remain an important area for future research

Comparison of different sets of immunological tests to identify treatable immunodeficiencies in adult bronchiectasis patients

BACKGROUND: The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis. METHODS: An observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests. RESULTS: A total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines. CONCLUSION: A four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines

Non-specific interstitial pneumonia and features of connective tissue disease: What are the consequences of a different point of view?

Patients with Interstitial Lung Disease (ILD) without a definitive diagnosis of connective tissue diseases (CTD) were historically described as Undifferentiated Connective Tissue Disease (UCTD-ILD). Recently a new classification, Interstitial Pneumonia with Autoimmune Features (IPAF), has been proposed. Aim of this study was to describe the prevalence, clinical characteristics and prognostic factors of UCTD and IPAF subjects in a cohort of Non-Specific Interstitial Pneumonia (NSIP) patients. This retrospective, observational study enrolled 102 adult patients characterized by NSIP pattern on High Resolution Computed Tomography, without a specific diagnosis of CTD. Three groups were identified according to patients’ characteristics: IPAF, UCTD or idiopathic NSIP (iNSIP). Forty percent, 27% and 55% of patients showed diagnostic criteria for IPAF, UCTD and iNSIP, respectively. No significant differences in age, gender, smoking habit, pulmonary function tests and three-year survival rate were observed among study groups. IPAF patients with antisynthetase antibodies positivity, in comparison to IPAF without antisynthetase antibodies positivity, showed more frequently an acute onset (44% vs 9%, p<0.012). The presence of autoimmune features seems not to be associated with better outcomes in NSIP patients. IPAF criteria seem to be more representative than UCTD criteria in identifying patients with autoimmune features. Further studies are needed to verify if IPAF should include patients with positive antisynthetase serology

Two-month acute microangiopathic brain injury follow-up in severe COVID-19: a case report

Coronavirus disease-19 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus-2 and was declared a pandemic in March 2020. It mainly causes upper respiratory symptoms, but an interstitial viral pneumonia may occur, in severe cases complicated by acute respiratory distress syndrome. Neurological involvement has been reported but has not been well investigated. A 75-year old man presenting with severe COVID-19 related pneumonia developed a severe cognitive impairment and a right temporal hemianopsia, with focal microangiopathy and subacute ischemic alterations detected on brain imaging, interpreted as vasculitic-inflammatory injury. The neurological disorder was diagnosed only after he was extubated. A rehabilitation program was set up, so the patient had a complete cognitive recovery. Our case underlines how COVID-19 can lead to severe neurological sequelae, so neurological examination should be promptly performed when patients display signs of nervous system involvement, in order to prevent further damages

Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review

Pirfenidone and nintedanib are antifibrotic medications approved for idiopathic pulmonary fibrosis treatment by regulatory agencies and available for clinical use worldwide. These drugs have been shown to reduce the rate of decline in forced vital capacity and the risk of acute exacerbation among patients with idiopathic pulmonary fibrosis. Recent data suggest that different interstitial lung diseases with a progressive pulmonary fibrosis phenotype can share similar pathogenetic and biological pathways and could be amenable to antifibrotic therapies. Indeed, historical management strategies in interstitial lung disease have failed to identify potential treatments once progression has occurred despite available drugs. In this systematic review, we summarized data on the efficacy of pirfenidone and nintedanib in interstitial lung diseases other than idiopathic pulmonary fibrosis as well as ongoing and upcoming clinical trials. We identify two well-designed trials regarding nintedanib demonstrating the efficacy of this drug in slowing disease progression in patients with interstitial lung diseases other than idiopathic pulmonary fibrosis. On the other hand, results on the use of pirfenidone in interstitial lung diseases other than idiopathic pulmonary fibrosis should be interpreted with more caution on the basis of trial limitations. Several randomized control trials are underway to improve the quality of evidence in the interstitial lung disease field

Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases

Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Pulmonary involvement includes interstitial lung disease in Gaucher&rsquo;s disease and Niemann-Pick disease, obstructive airway disease in Fabry disease and ventilatory disorders with chronic respiratory failure in Pompe disease due to diaphragmatic and abdominal wall muscle weakness. In mucopolysaccharidosis and mucolipidoses, respiratory symptoms usually manifest early in life and are secondary to anatomical malformations, particularly of the trachea and chest wall, and to accumulation of glycosaminoglycans in the upper and lower airways, causing, for example, obstructive sleep apnea syndrome. Although the molecular pathways involved vary, ranging from lipid to glycogen and glycosaminoglycans accumulation, some clinical manifestations and therapeutic approaches are common among diseases, suggesting that lysosomal storage and subsequent cellular toxicity are the common endpoints

Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats

Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and/or oxidative events. Materials and methods: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL/kg/h) or RR (30 mL/kg/h for 40 min, followed by 75 mL/kg/h) with Ringer&rsquo;s solution (n = 8/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Results: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 &plusmn; 420 vs. 724 &plusmn; 75 AU) and in liver (474 &plusmn; 57 vs. 261 &plusmn; 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p &lt; 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 &plusmn; 2 vs. 14 &plusmn; 0.5 RLU). Conclusion: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and/or oxidative stress reactions

Genetic and Serum Screening for Alpha-1-Antitrypsin Deficiency in Adult Patients with Cystic Fibrosis: A Single-Center Experience

Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two of the commonest genetic diseases affecting the Caucasian population. Neutrophil-mediated inflammation due to protease&ndash;antiprotease imbalance leads to progressive pulmonary involvement in both diseases. The aim of this study was to investigate the prevalence of AAT deficiency in CF adults. A prospective study enrolling CF adults was conducted at the Adult CF Center based in Milan from January 2018 to March 2019. Patients were tested for AAT serum protein quantification and expanded genotyping characterization of SERPINA1 during clinical stability. Genotyping characterization of SERPIN1 was compared to a control population of 2848 Caucasian individuals with the same geographical origin and similar demographic characteristics. Among 173 patients included in the study, the prevalence of AAT deficiency was 0. Genotype analysis was piMM in 166 (94.9%) patients and piMS in 9 patients (5.1%), respectively. No differences in terms of genotype characterization were found between the CF population and the control population. These data show that AAT deficiency is not common among adults with CF