Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Joint Statement on the Role of Respiratory Rehabilitation in the COVID-19 Crisis: The Italian Position Paper.

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning for COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which are described in this paper to face the emergency.

Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging.

Cognitive Deficits among Individuals Admitted to a Post-Acute Pneumological Rehabilitation Unit in Southern Italy after COVID-19 Infection.

(1) Background: We investigated the differences in the neuropsychological profile as well as the pneumological and motor functions in two groups of patients admitted to rehabilitation who received different respiratory support during their COVID-19 infection. (2) Methods: Group-1 (n = 18; 15 male, median age 67.5) consisted of patients who received non-invasive mechanical ventilation; Group-2 (n = 19; 16 male, median age 63) consisted of patients who received invasive mechanical ventilation. All patients underwent a neuropsychological assessment including Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and the Repeatable Battery for the Assessment of Neuropsychological Status (R-BANS) to evaluate the patients' cognition. Depression and anxiety were also measured at admission and discharge to rehabilitation. (3) Results: At admission, patients impaired at MMSE were 44% in Group-1 and 5% in Group-2, while patients impaired at FAB were 88% in Group-1 and 26% in Group-2. Wilcoxon's effect size revealed meaningful differences between groups for FAB, R-BANS global score, immediate and delayed memory, and attention-coding task, with Group-2 performing better than Group-1 across all measures. At discharge, 52% of the 25 patients re-assessed still had mild to moderate cognitive deficits, while 19% had depression and 35% had anxiety. (4) Conclusions: Patients who received oxygen therapy experienced higher levels of acute and chronic stress compared to those who benefitted from invasive mechanical ventilation. Despite patients showing a meaningful improvement at discharge, cognitive impairment persisted in a great number of patients; therefore, long-term neuropsychological follow-up and treatment for COVID-19 patients are recommended.

The association between dysphagia and OSA.

OBJECTIVE: The aim of our study was to investigate the presence of dysphagia in patients with Obstructive Sleep Apnoea (OSA) and to correlate swallowing impairment with hypnologic and anatomic parameters. METHODS: The study population includes 36 patients suffering from OSA. Patients were divided into two groups using the presence of dysphagia as a distinctive parameter. Group 1 included 27 OSA patients without signs of dysphagia and Group 2 included 9 OSA patients with signs of dysphagia. RESULTS: The age of patients in Group 2 was higher compared with the age of patients in Group 1. Analysis of Continuous Positive Airway Pressure (CPAP), obtained in the titration phase, showed that OSA patients with signs of dysphagia required a higher level of CPAP pressure than those who were not affected by swallowing abnormalities (12.6 ± 1 vs 10.5 ± 1.9 p = 0.003). No other differences in anthropometric, hypnologic, or arterial blood gas values were found between the two groups. CONCLUSIONS: In clinical practice, all OSA patients should undergo a complete ENT exam, including assessment of swallowing, before CPAP therapy is started. This may predict the need for higher CPAP pressure settings to resolve apnoea episodes in the presence of dysphagia as well as guide the choice of CPAP interfaces (orofacial vs. nasal) in these patients.

Age and comorbidities are crucial predictors of mortality in severe obstructive sleep apnoea syndrome.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent disorder. The prognostic role of comorbidity in patients with OSAS and their role for risk stratification remain poorly defined. METHODS: We studied 1,592 patients with severe OSAS diagnosed by polysomnography. The primary outcome was all-cause mortality. The standardized mortality ratio (SMR) was estimated as the ratio of observed deaths to expected number of deaths in the general population. The expected numbers of deaths were derived using mortality rates from the general Apulian population. The association of comorbidities with all-cause mortality was assessed using multivariable Cox regression analysis. Finally, recursive-partitioning analysis was applied to identify the combinations of comorbidities that were most influential for mortality and to cluster the patients into risk groups according to individual comorbidities RESULTS: During 11,721 person-years of follow-up, 390 deaths (3.33 deaths/100 person-years) occurred. The median follow-up was 7 (4-10) years. The SMR was 1.47 (95% confidence intervals 1.33-1.63). Age, sex, obesity, cardiovascular diseases (CVD), moderate-to-severe chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and malignancy were independently associated with mortality risk. Recursive-partitioning analysis allowed distinguishing three clinical phenotypes differentially associated with mortality risk. The combination of CKD with CVDs or with moderate-to-severe COPD conferred the highest risk. CONCLUSIONS: Severe OSAS is associated with increased risk for all-cause death. Age and comorbidity are crucial predictors of mortality in patients with severe OSAS. Clustering patients according to comorbidities allows identifying clinically meaningful phenotypes.

Incidence of deep venous thrombosis in patients with both Pulmonary Embolism and COPD.

BACKGROUND: There are no studies investigating populations of patients with both pulmonary embolism and chronic obstructive pulmonary disease (PE-COPD) with and without deep venous thrombosis (DVT). AIM OF THE STUDY: To define prevalence of DVT in COPD with PE and to compare characteristics of COPD patients who develop PE, with and without DVT. Secondly, we aimed to assess differences in the localization of PE among study groups.  METHODS. 116 patients with PE were enrolled in a retrospective study. Clinical data as well as echocardiographic and lower limb ultrasonography records were collected for all subjects. Subjects were divided into two groups according to the presence of COPD: Group 1, 54 patients with diagnosis of PE without COPD and Group 2, 66 patients diagnosed of PE with  COPD. Then, individuals of Group 2 were subdivided in two subgroups according to the presence (n=21) or absence (n=45) of DVT. RESULTS: 33% of patients with COPD and PE showed DVT.  These subjects had higher PaCO2 and ejection fraction (p<0.05 for all) and higher percentage of chronic renal failure and diabetes mellitus compared to those without DVT (p<0.05 for all). Moreover, in COPD-PE patients with DVT, the most frequent localization was proximal (54% of total), whereas COPD-PE patients without DVT showed a more frequent segmental localization (60% of total). No difference was found in clinical presentation and blood-chemistry tests. CONCLUSIONS: DVT was non-common in PE-COPD patients. Chronic renal failure, and type 2 diabetes mellitus are more frequent in PE-COPD patients with DVT, that showed a higher frequency of proximal localization, thereby indicating a greater risk of more severe clinical implications. Conversely, PE- COPD subjects without DVT showed a more frequent segmental localization and were less hypercapnic. PE should be taken into account in COPD with worsening of respiratory symptoms, also in absence of DVT.

Reduction of Sniff Nasal Inspiratory Pressure (SNIP) as an Early Indicator of the Need of Enteral Nutrition in Patients with Amyotrophic Lateral Sclerosis.

Percutaneous endoscopic gastrostomy (PEG) is the standard procedure for feeding severely dysphagic patients with amyotrophic lateral sclerosis (ALS). It is associated with prolonged survival and improvement in quality of life. Nasal inspiratory pressure during a sniff (SNIP) is a respiratory test used extensively in ALS for the assessment of inspiratory muscle strength. In this study, we aimed to investigate the role of SNIP at baseline to predict PEG placement in ALS. Data from a clinical incident cohort of 179 ALS cases attending the multidisciplinary ALS unit of the University of Bari between April 2006 and December 2012 were retrospectively analysed. At baseline, patients underwent detailed neurological, nutritional and respiratory assessments, including measurements of SNIP and forced vital capacity (FVC). Patients were therefore followed up approximately every three to six months until they were able to attend the centre. The censoring date for the survival analysis was 15 April 2014, with PEG placement as the main outcome. Cox proportional hazard regression models were used to examine the association between SNIP and PEG placement, adjusted for possible confounders. During the follow-up period, 75 participants (42%) received PEG implant. PEG placement was more frequent (57% vs. 31%; p = 0.001) and earlier (after 11.6 ± 14.0 months from the first visit, vs. 23.3 ± 15.5 months; p < 0.0001) in the group of patients with baseline SNIP ≤ 40 cm H2O. Baseline SNIP was a predictor of PEG placement even after correction for multiple potential confounders (HR 0.98; 95% CI: 0.96-0.99; p = 0.02). To conclude, the present study showed that SNIP at baseline is an early indicator of disease progression and therefore of the need for enteral nutrition in ALS.

Galectin-3 and neutrophil-to-lymphocyte ratio are indicative of heart remodelling and disease severity in patients with obstructive sleep apnoea.

BACKGROUND: Galectin-3, considered as a new inflammatory marker; it is increased in cardiovascular disease. We investigated Galectin-3 in relation to heart damage in patients with OSA and its role in inflammation, based on the Neutrophil-to-Lymphocyte Ratio (NLR). METHODS: Sixty-three consecutive patients (45 males, 18 females, 58.60 ± 12.28 years old) were studied. According to the Apnoea-Hypopnoea Index (AHI) patients were divided into Group 1 - non-severe (AHI <30) (17 males and 10 females, 59.89 ± 10.62 years old) and Group 2 - severe (AHI ≥30) (29 males and 6 females, aged 57.53 ± 13.30 years old) OSA. All patients underwent morning blood gas analysis, laboratory tests, nocturnal polygraphy, and echocardiography. RESULTS: Galectin-3 was significantly increased in Group 2 (p = 0.027) patients. Moreover, it was directly related to left ventricle (LV) mass, left ventricle hypertrophy and LV posterior wall diameter. Tissue Doppler septal velocity (e'), that measures wall motion, was inversely correlated to Galectin-3. Furthermore, a direct association to diastolic dysfunction, evaluated as E/e' ratio, was observed. In line with these data, a direct correlation between Galectin-3 and left atrium volume was also found. Galectin-3 and percentage of total registration time with nocturnal oxygen saturation <90% (TST90) were directly correlated (p = 0.0003), while Galectin-3 and mean nocturnal SpO2 were negatively correlated (p = 0.0045). We found a direct correlation between Galectin-3 and NLR (p = 0.011). Finally, Galectin-3 was able to predict 3-yr mortality with a specificity of 83.33% and a sensitivity of 91.84%. CONCLUSION: Galectin-3 showed a direct association to nocturnal respiratory indices and to cardiac remodelling in patients with OSA. OSA-induced inflammation may play an important role in the pathogenesis of heart damage.

An unusual spirometric shape that you must not forget.

An anomalous spirometric pattern can initiate a diagnostic path leading to the finding of a congenital vascular malformation. The flow-volume curve may hide a nonrespiratory pathology. Spirometry is not just asthma or COPD. http://bit.ly/30iHRCp.

Inhaled Corticosteroids And Risk Of Tuberculosis In Patients With Obstructive Lung Diseases: A Systematic Review And Meta-Analysis Of Non-randomized Studies.

Background: An association between systemic corticosteroids and tuberculosis (TB) is reported in the literature. Here within, we conducted a systematic review and meta-analysis to evaluate the effects of inhaled corticosteroids (ICS) on the risk of TB in patients with obstructive lung diseases. Methods: The review was registered on PROSPERO (CRD42018095874). PubMed, CENTRAL, Scopus and Web of Science were searched from inception to September 2018. Papers reporting cases of incident TB in patients with obstructive lung diseases were included; studies without data on ICS use were excluded. Simultaneous use of oral corticosteroids (OCS) and population attributable fraction (PAF) for TB from ICS exposure were also assessed. Data were analyzed using a generic inverse variance method with a random-effects model. ORs with 95% CI were estimated. Results: Out of 4044 retrieved papers, 9 articles evaluating adult patients only were included in the review. 36,351 patients were prescribed ICS, while 147,171 were not. Any ICS use was associated with an increased risk of TB versus no ICS use (OR=1.46; 95% CI 1.06 to 2.01; p=0.02; I2=96%). A similar result was also found for current ICS use versus prior/no ICS use, as well as for high, moderate and low ICS dose versus no ICS. When simultaneous OCS use was evaluated, the independent contribution of ICS was confirmed only in patients not on OCS (OR=1.63; 95% CI 1.05 to 2.52; p=0.03; I2=94%). Only 0.49% of all TB cases could be attributable to ICS exposure. Conclusions: Despite the association between ICS and TB, the contribution of this risk factor to the epidemiology of TB seems to be limited. As a consequence, no population-based interventions are warranted. Rather, this risk should be taken into account on an individual basis, particularly in those patients with a high risk of progression from LTBI to TB.

Effects of CPAP on Testosterone Levels in Patients With Obstructive Sleep Apnea: A Meta-Analysis Study.

Background: Obstructive sleep apnea (OSA) represents a frequent complication among patients with obesity and has been associated with neuroendocrine changes, including hypogonadism. Objective: We conducted a systematic review and meta-analysis to evaluate the effects of continuous positive airway pressure (CPAP) on testosterone and gonadotropins in male patients with OSA. Methods: The review was registered on PROSPERO (CRD42018103164). PubMed, Scopus, CENTRAL, and Clinicaltrials.gov were searched until June 2018. Studies reporting the effect of CPAP on total testosterone, free testosterone, sexual hormone binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), and prolactin were included. A subgroup analysis on hypogonadal vs. eugonadal status at baseline was performed. Results: Out of 129 retrieved papers, 10 prospective cohort and 2 randomized controlled studies were included in the review. Three hundred eighty-eight patients were included. CPAP use was not associated with a significant change in total testosterone levels [mean difference 1.08, 95% confidence interval (CI) -0.48 to 2.64] or other outcomes. The subgroup analysis confirmed the overall results. Conclusions: The present review does not support the hypothesis of a direct interaction between OSA and testosterone. Strategies other than CPAP should therefore be considered in managing hypogonadism in patients with OSA.

Nocturnal Hypoventilation May Have a Protective Effect on Ischemic Heart Disease in Patients with Obesity Hypoventilation Syndrome.

The importance of nocturnal hypoventilation (nHyp) in the development of cardiovascular comorbidity (CVM) in patients with obesity hypoventilation syndrome (OHS) is controversial. We recently hypothesized that nHyp may have a protective effect on CVM in OHS. The aim of this study was to evaluate the link between nHyp and CVM in patients with OHS. We performed a retrospective analysis of the clinical records of 60 patients with OHS. The initial population was divided into two groups: (1) 31 subjects with OHS and nHyp (nhOHS); (2) 29 individuals with OHS without nHyp (wnhOHS). All patients had also obstructive sleep apnea. Anthropometric data, medical history, electrocardiogram, pulmonary function testing, arterial blood gas test, and sleep recordings were collected. Patients with nhOHS, compared with those wnhOHS, showed higher values of PaCO2 (48.75 ± 3.78 vs. 46.91 ± 2.09 mmHg; p = 0.023), lower percentage of ischemic heart disease (3.2% vs. 20.7%; p = 0.042), higher oxygen desaturation index (ODI; 55.10/h ± 28.76 vs. 38.51/h ± 23.21; p = 0.017), and higher total sleep time (TST90) with SpO2 <90% (53.58% ± 26.90 vs. 25.64% ± 21.67; p = 0.000). Moreover, individuals in the nhOHS group showed a significantly different (p = 0.031) distribution of the three ODI tertiles 0-32/h, 33-72/h, >72/h compared with those in wnhOHS group (19.4% vs. 37%, 41.9% vs. 51.7%, 38.7% vs. 10.3%, respectively). Subsequent discriminant analysis correctly classified nhOHS and wnhOHS in 66.7% of the cases. Ours is the first study analyzing the correlation between nHyp and CVM in patients with OHS. We showed that nHyp in OHS may have a protective effect on cardiovascular morbidity, in particular on ischemic cardiac disease.

Bilateral pulmonary nodules and acute respiratory failure in a 22-year-old man with dyspnoea and fever.

Can you diagnose the cause of this man's bilateral pulmonary nodules and acute respiratory failure? http://ow.ly/NfED30dDBzm.

Voluntary lung function screening to reveal new COPD cases in southern Italy.

BACKGROUND: Underdiagnosis of COPD is a relevant issue, and most frequently involves patients at early stages of the disease. Physicians do not routinely recommend smokers to undergo spirometry, unless they are symptomatic. AIMS: To investigate the effectiveness of voluntary lung function screening in bringing to light patients with previously unknown COPD and to evaluate the relationships among symptoms, smoking status, and airway obstruction. METHODS: A voluntary screening study for COPD was conducted during two editions of the annual Fiera del Levante (2014 and 2015), an international trade fair in Bari. Subjects were eligible for the study if they fulfilled the following inclusion criteria: age ≥35 years, smoker/ex-smoker ≥5 pack-years (PYs), or at least one chronic respiratory symptom (cough, sputum production, shortness of breath, and wheezing). A free post-ß2-agonist spirometry test was performed by trained physicians for each participant using portable spirometers. Post-ß2-agonist forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative and positive predictive values (NPVs and PPVs) of symptoms for the presence of obstruction were calculated. RESULTS: A total of 1,920 individuals were eligible for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4% prevalence of COPD in subjects with one or more symptoms who had never smoked or smoked ≤5 PYs. Among COPD patients, prevalence of symptoms increased in the presence of FEV1 <80%. COPD smokers were more symptomatic than smokers without COPD. Sensitivity and specificity in all subjects with one or more symptoms were 87% and 32%, respectively, whereas in smoker subgroups, sensitivity and specificity were 71% and 41% (≥5 PYs) and 74% and 35% (≥10 PYs), respectively. In all subjects, the presence of at least one symptom was associated with a low PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the analysis was limited to smokers. CONCLUSION: Voluntary public lung function screening programs in Italy are effective, and may detect a large number of undiagnosed subjects with COPD in early stages. In our population, COPD symptoms had low specificity and PPV, even considering smokers only.

Clinical and Functional Lung Parameters Associated With Frequent Exacerbator Phenotype in Subjects With Severe COPD.

BACKGROUND: COPD is currently recognized as a syndrome associated with a high prevalence of comorbidities and various phenotypes. Exacerbations are very important events in the clinical history of COPD because they drive the decline in lung function. In the present study, we aim to identify whether there are any clinical and functional specific features of frequent exacerbators in a population of patients with severe COPD. METHODS: We conducted a cross-sectional, case control study. All subjects had Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 3 or 4 COPD (FEV1 < 50% predicted). Frequent exacerbators (n = 183) reported ≥2 exacerbations or ≥1 determining hospitalization during the previous 12 months, and infrequent exacerbators (n = 162) reported <2 exacerbations over the last 12 months without hospitalization. Multivariate logistic regression was performed to determine the clinical and functional factors significantly associated with frequent exacerbator status. RESULTS: Frequent exacerbators had a significantly lower inspiratory capacity percentage predicted. The Motley index (residual volume/total lung capacity percentage) was significantly increased in frequent exacerbators. Infrequent exacerbators had lower Modified Medical Research Council dyspnea scale and BODE index than frequent exacerbators. In the multivariate model, a reduced inspiratory capacity percentage predicted and an increase of residual volume/total lung capacity percentage, BODE index and Modified Medical Research Council dyspnea scale were associated with the frequent exacerbation phenotype. CONCLUSIONS: Static hyperinflation and respiratory disability, measured by Motley index and Modified Medical Research Council dyspnea scale, respectively, in the same way as the multidimensional BODE index staging system, were independently associated with frequent exacerbation status in subjects with severe COPD.

Pulmonary nocardiosis in Chronic Obstructive Pulmonary Disease: A new clinical challenge.

Pulmonary nocardiosis (PN) is a rare but severe disease caused by Nocardia spp. Despite the traditional description as opportunistic infection, case reports and case series of pulmonary nocardiosis have recently been reported in immunocompetent patients too, in particular among people with chronic pulmonary diseases such as advanced Chronic Obstructive Pulmonary Disease (COPD). PN is characterized by non-specific symptoms and radiological findings; bacteriological culture can be difficult. For the reasons above, diagnosis of PN is challenging, sometimes resulting in a misdiagnosis of tuberculosis. We report an interesting case of PN in a 75-year-old male with COPD. He complained a 3-months history of fatigue, evening rise in body temperature, night sweats, unexplained weight loss of 5 kg, worsening dyspnea, cough and mucopurulent sputum. The chest X-ray showed multiple nodules with cavitations bilaterally in the apical and subclavian regions. Nocardia cyriacigeorgica with 100% identity was identified in three sputum samples. Since the patient has never undergone a systemic and/or inhaled steroid therapy, and has no respiratory failure and comorbidities entailing immunodepression, it is conceivable that, in this immunocompetent patient, the COPD could represent an isolated risk factor for PN. Risk factors, clinical presentations, radiographic findings, differential diagnosis and review of the literature of PN cases in COPD, pointing out the similarities and differences, are also described.

Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells. The present study explores the epidemiological, familial, genetic, clinical, diagnostic, radiological and therapeutic aspects with the aim of contributing to a better understanding of this uncommon disease.We searched articles on PAM published up to December 2014 and 544 papers were found, accounting for 1022 cases.PAM is present in all continents and in many nations, in particular in Turkey, China, Japan, India, Italy and the USA. Familiality is frequent. The clinical course is not uniform and the causes of this clinical variability seem to be largely nongenetic. The optimal diagnostic procedure is the association of chest high-resolution computed tomography (HRCT) with bronchoalveolar lavage, but a chest radiograph may suffice in families in which a case has already been diagnosed. Moreover, chest radiography and HRCT allow the classification of the evolutionary phase of the disease and its severity. At present lung transplantation is the only effective therapy. However, better knowledge of the gene responsible offers hope for new therapies.