The effect of Borago officinalis on the signaling pathway of the NLRP3 inflammasome complex, TLR4 and some inflammatory cytokines in type II diabetic patients with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition in which the lungs become severely inflamed, causing the alveoli to constrict or fill with fluid, which prevents the lungs from functioning properly. This disease becomes more dangerous when it occurs in patients with diabetes. Because of the clinical condition of these patients, it is not possible to treat them with usual medicines. One of the best options for treating these people is to use herbs. Borage (Borago officinalis) is a medicinal herb that, in addition to its anti-inflammatory properties, is also able to control blood sugar. Therefore, in the current study, the effect of borage oil was considered on the signaling pathway of the NLRP3 inflammasome complex, TLR4, and serum levels of inflammatory cytokines (IL-1? and IL-18) in type II diabetic patients with ARDS. For this purpose, 25 diabetic type II patients with ARDS were divided into three groups by ARDS Berlin Definition. Then, after providing the demographic and clinical characteristics of the patients, they were treated with 30 mg/day borage oil for seven days. The expression of NLRP3 and TLR4 genes (by Real-time PCR technique) and serum levels of IL-1? and IL-18 (by ELISA test) were evaluated before and after treatment with borage oil through blood samples taken from patients. The results showed that serum levels of inflammatory cytokines (IL-1? and IL-18), NLRP3 gene, and TLR4 gene were significantly decreased in diabetic type II patients with mild ARDS by treating with borage oil. IL-1? serum level and TLR4 were significantly decreased in diabetic type II patients with moderate ARDS. But there was not any significant decrease or increase in IL-1?, IL-18, NLRP3 gene, and TLR4 gene in diabetic type II patients with severe ARDS after 7 days of treatment with borage oil. According to the obtained results, borage oil can act as a double-edged blade. Thus, in the early and middle stages of ARDS, borage oil can be effective in reducing the inflammasome pathway of inflammation and also reduce blood sugar levels in these diabetic patients. But in the severe stage of ARDS, it not only does not help to treat the ARDS; it also increases systolic and diastolic blood pressure in diabetic patients.

Treating ARDS-associated air embolism: a question of priorities.

Gas embolism is a potential and often life-threatening complication of central venous catheters. We report a case of air embolism after tearing of the central catheter associated with severe acute respiratory distress syndrome. The severity of the clinical situation meant choices had to be made regarding the order of treatments. This clinical case provided useful eye-openers for patient management regarding the prioritization of treatments as well as the possibilities offered by hyperbaric oxygen therapy.

Scientific Rationale for a Bottom-Up Approach to Target the Host Response in Order to Try and Reduce the Numbers Presenting With Adult Respiratory Distress Syndrome Associated With COVID-19. Is There a Role for Statins and COX-2 Inhibitors in the Prevention and Early Treatment of the Disease?

The inflammatory response to and the subsequent development of Adult Respiratory Distress Syndrome (ARDS) is considered to underpin COVID-19 pathogenesis. With a developing world catastrophe, we need to examine our known therapeutic stocks, to assess suitability for prevention and/or treatment of this pro-inflammatory virus. Analyzing commonly available and inexpensive immunomodulatory and anti-inflammatory medications to assess their possible effectiveness in improving the host response to COVID-19, this paper recommends the following: (1) optimize current health-cease (reduce) smoking, ensure adequate hypertension and diabetes control, continue exercising; (2) start on an HMG CoA reductase inhibitor "statin" for its immunomodulatory and anti-inflammatory properties, which may reduce the mortality associated with ARDS; and (3) consider using Diclofenac (or other COX-2 inhibition medications) for its anti-inflammatory and virus toxicity properties. For purposes of effectiveness, this needs to be in the early course of the disease (post infection and/or symptom presentation) and given in a high dose. The downsides to these recommended interventions are considered manageable at this stage of the pandemic.

COVID-19 and Vitamin D: A lesson from the skin.

The negative outcomes of COVID-19 diseases respiratory distress (ARDS) and the damage to other organs are secondary to a "cytokine storm" and to the attendant oxidative stress. Active hydroxyl forms of vitamin D are anti-inflammatory, induce antioxidative responses, and stimulate innate immunity against infectious agents. These properties are shared by calcitriol and the CYP11A1-generated non-calcemic hydroxyderivatives. They inhibit the production of pro-inflammatory cytokines, downregulate NF-κΒ, show inverse agonism on RORγ and counteract oxidative stress through the activation of NRF-2. Therefore, a direct delivery of hydroxyderivatives of vitamin D deserves consideration in the treatment of COVID-19 or ARDS of different aetiology. We also recommend treatment of COVID-19 patients with high-dose vitamin D since populations most vulnerable to this disease are likely vitamin D deficient and patients are already under supervision in the clinics. We hypothesize that different routes of delivery (oral and parenteral) will have different impact on the final outcome.

Novel coronavirus 2019 (COVID-19): A case report and review of treatments.

RATIONALE: Novel coronavirus 2019 (COVID-19) also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, non-segmented positive-sense RNA virus belonging to the beta-coronaviridae family. This virus is known to cause severe bilateral pneumonia and acute respiratory distress syndrome (ARDS) which can lead to difficulty breathing requiring mechanical ventilation and intensive care unit management. PATIENT CONCERNS: A 77-year-old female with a history of hypertension and hyperlipidemia who presented as a transfer to our hospital facility with worsening fevers, cough, and respiratory distress. DIAGNOSIS: Chest X-rays revealed bilateral infiltrates worse at the lung bases and CT scan of the chest showed bilateral ground-glass opacities consistent with COVID-19. While our testing revealed a negative COVID-19 result at our institution, the result at a previous hospital returned a positive result. INTERVENTIONS: She was being treated aggressively in the intensive care unit with high dose intravenous ascorbic acid, hydroxychloroquine, and anti-interleukin-6 monoclonal antibody. She also received a loading dose of remdesivir however was unable to complete the course due to organ failure and requirement of vasopressors for hemodynamic stability. OUTCOMES: She remained critically ill and was eventually placed on comfort care as per the family's wishes and passed away. LESSONS: With a rapidly growing death rate and more than 200,000 confirmed cases worldwide, COVID-19 has become a global pandemic and major hit to our healthcare systems. While several companies have already begun vaccine trials and healthcare facilities have been using a wide-range of medications to treat the virus and symptoms, there is not yet an approved medication regimen for COVID-19 infections. The alarming increase in cases per day adds additional pressure to find a cure and decrease the global health burden and mortality rate.

Efficacy of blood purification for severe pancreatitis and acute respiratory distress syndrome.

BACKGROUND: This study will assess the efficacy and safety of blood purification (BP) for severe pancreatitis (SP) and acute respiratory distress syndrome (ARDS). METHODS: We will search the following electronic databases of Ovid MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, and WANGFANG from inception to the present without language restriction. A systematic review and data synthesis will be carried out of randomized controlled trials of BP for the treatment of patients with SP and ARDS. RevMan 5.3 software will be used for statistical analysis. RESULTS: This systematic review will evaluate the efficacy and safety of BP for the treatment of patients with SP and ARDS. The primary outcome includes respiratory indexes, blood biochemical and inflammatory factors. The secondary outcomes consist of complications, sepsis, abdominal hemorrhage, renal failure, length of hospital stay, and mortality. CONCLUSION: This study will provide up-to-date evidence of BP for the treatment of patients with SP and ARDS. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019139467.

Should Immune-Enhancing Formulations Be Used for Patients With Acute Respiratory Distress Syndrome?

The potential for regulating immune function in acute respiratory distress syndrome (ARDS) through enteral-administered anti-inflammatory lipids has generated much interest over the past 20 years. Yet recommendations remain inconclusive regarding the utilization of ω-3 fatty acids in patients with ARDS and acute lung injury (ALI). Studies are limited in number, with differing methods, small sample sizes, and conflicting results, making recommendations difficult to interpret.

Increased Risk of Post-Trauma Stroke after Traumatic Brain Injury-Induced Acute Respiratory Distress Syndrome.

This study determines whether acute respiratory distress syndrome (ARDS) is an independent risk factor for an increased risk of post-traumatic brain injury (TBI) stroke during 3-month, 1-year, and 5-year follow-ups, respectively, after adjusting for other covariates. Clinical data for the analysis were from the National Health Insurance Database 2000, which covered a total of 2121 TBI patients and 101 patients with a diagnosis of TBI complicated with ARDS (TBI-ARDS) hospitalized between January 1, 2001 and December 31, 2005. Each patient was tracked for 5 years to record stroke occurrences after discharge from the hospital. The prognostic value of TBI-ARDS was evaluated using a multivariate Cox proportional hazard model. The main outcome found that stroke occurred in nearly 40% of patients with TBI-ARDS, and the hazard ratio for post-TBI stroke increased fourfold during the 5-year follow-up period after adjusting for other covariates. The increased risk of hemorrhagic stroke in the ARDS group was considerably higher than in the TBI-only cohort. This is the first study to report that post-traumatic ARDS yielded an approximate fourfold increased risk of stroke in TBI-only patients. We suggest intensive and appropriate medical management and intensive follow-up of TBI-ARDS patients during the beginning of the hospital discharge.

A case of Mediterranean spotted fever associated with severe respiratory distress syndrome.

Mediterranean spotted fever (MSF) is usually a mild endemic rickettsial disease occurring in southern Croatia. We have reported the clinical and epidemiological characteristics of an acute MSF case associated with severe respiratory distress syndrome and hemodynamical instability. The patient recovered completely after antimicrobial treatment. Indirect immunofluorescence assay (FOCUS Diagnostics Inc.) was performed to detect IgM and IgG antibodies to Rickettsia conorii. A significant increase of both IgM and IgG antibody titres found in paired acute- and convalescent-phase serum confirmed the diagnosis of acute MSF.

[Acute respiratory distress syndrome complicating an acute chest syndrome: potential benefit of early combination of exchange transfusion and prone positioning]. / Syndrome de défaillance respiratoire aiguë sévère au cours d'un syndrome thoracique aigu chez une enfant drépanocytaire de 8ans : bénéfice potentiel de l'association précoce échange transfusionnel et décubitus ventral.

We report the case of an 8-year-old sickle cell anemia child admitted for acute respiratory failure complicating acute chest syndrome. Because of threatening respiratory failure, tracheal intubation was performed immediately after ICU admission. The patient met the criteria for ARDS with a PaO2/FiO2 ratio of 94mmHg. An exchange transfusion was performed immediately after admission. HbS fraction failed from 69 % to 30 %. Fluid resuscitation with crystalloids and continuous norepinephrine infusion was needed because of arterial hypotension. Due to persistent severe hypoxemia with PaO2/FiO2 ratio below 100, the patient was placed in prone positioning 16hours after admission, for a total duration of 14hours. A second 12-hour session of prone positioning was performed 41h after admission and PaO2/FiO2 ratio reached 300mmHg after. Treatment also included transfusion of two red-cell pack on day 1 and 2 after admission in order to maintain hemoglobin level above 8g/dL, and a daily folic acid supplementation. The control of hyperthermia was achieved by a systematic parenteral administration of paracetamol. Cefotaxime and erythromycine were continued until day 7 despite the negative results of all bacteriological samples. The outcome was favorable from day 3 and the patient met the criteria for extubation on day 5. A first attempt of extubation was performed on day 5, but re-intubation was required because of laryngeal edema. Steroids were given for 48h and the patient was successfully extubated on day 7. She was discharged from the ICU on day 8, and from the hospital on day 12. We discuss the various treatments available for the management of acute chest syndrome and their actual relevance in acute respiratory distress syndrome in the absence of strong evidence-based guidelines in pediatric ARDS.

Biological therapies in the acute respiratory distress syndrome.

INTRODUCTION: The acute respiratory distress syndrome (ARDS) is characterised by life-threatening respiratory failure requiring mechanical ventilation, and multiple organ failure. It has a mortality of up to 30 - 45% and causes a long-term reduction in quality of life for survivors, with only approximately 50% of survivors able to return to work 12 months after hospital discharge. AREAS COVERED: In this review we discuss the complex pathophysiology of ARDS, describe the mechanistic pathways implicated in the development of ARDS and how these are currently being targeted with novel biological therapies. These include therapies targeted against inflammatory cytokines, mechanisms mediating increased alveolar permeability and disordered coagulation, as well as the potential of growth factors, gene therapy and mesenchymal stem cells. EXPERT OPINION: Although understanding of the pathophysiology of ARDS has improved, to date there are no effective pharmacological interventions that target a specific mechanism, with the only potentially effective therapies to date aiming to limit ventilator-associated lung injury. However, we believe that through this improved mechanistic insight and better clinical trial design, there is cautious optimism for the future of biological therapies in ARDS, and expect current and future biological compounds to provide treatment options to clinicians managing this devastating condition.

[Pharmacological therapies for ARDS].

Acute respiratory distress syndrome (ARDS) is a noncardiogenic pulmonary edema resulting from increased capillary permeability. Numerous pharmacologic therapies have been studied for prevention and treatment of ARDS. Although several pharmacological therapies could improve patient's respiratory function, there have been no controlled studies which clearly demonstrated the clinical benefit for ARDS-related mortality. The role of corticosteroids in ARDS remains controversial. Available evidence is against early administration of high-dose corticosteroids (methylprednisolon 120 mg x kg-1 x day - 1). In contrast, low-dose corticosteroid therapy (methylprednisolon 0.5-2.5mgg kg-1 xday-1)remains controversial. With regard to sivelestat sodium, a specific inhibitor of neutrophil elastase, although the effectiveness in decreasing mortality was not clarified, increases in lung oxygenation and ventilator-free days have consistently been revealed. Other probable pharmacologic therapies for ARDS include continuous infusion of cisatracurium. In conclusion, there are not established drugs for ARDS, and further studies are necessary to reveal the clinical effectiveness of the above mentioned and novel pharmacologic therapies.

No additive effects of inhaled iloprost and prone positioning on pulmonary hypertension and oxygenation in acute respiratory distress syndrome.

BACKGROUND: In acute respiratory distress syndrome (ARDS), pulmonary hypertension is associated with a poor prognosis. Prone position is effective to improve oxygenation whereas inhaled iloprost can treat pulmonary hypertension. However, combination of these interventions has not been examined before. The hypothesis was that this combination had additive effects on oxygenation and pulmonary hemodynamics as compared with each intervention alone. METHODS: In a prospective, randomized cross-over study, ten pigs were anesthetized, intubated and ventilated with volume controlled ventilation. Carotid, jugular venous and pulmonary artery catheters were inserted. ARDS was induced with oleic acid (0.20 mL/kg). Measurements were repeated in randomized different sequences of prone or supine positions with or without iloprost inhalation (220 ng/kg/min) (four combinations). Systemic and pulmonary arterial pressures; arterial and mixed venous blood gases; and Qs/Qt and the resistances were recorded. RESULTS: Iloprost decreased pulmonary artery pressures (for MPAP: P=0.034) in both supine (37±10 vs. 31±8 mmHg; P<0.05) and prone positions (38±9 vs. 29±8 mmHg; P<0.05); but did not obtain a significant improvement in oxygenation in both positions. Prone position improved the oxygenation (p<0.0001) compared to supine position in both with (361±140 vs. 183±158 mmHg, P<0.05) or without iloprost application (331±112 vs. 167±117 mmHg, P<0.05); but did not achieve a significant decrease in MPAP. CONCLUSION: Although iloprost reduced pulmonary arterial pressures, and prone positioning improved oxygenation; there are no additive effects of the combination of both interventions on both parameters. To treat both pulmonary hypertension and hypoxemia, application of iloprost in prone position is suggested.

Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Insuficiencia respiratoria / Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): Respiratory failure

La insuficiencia respiratoria aguda grave que precisa ventilación mecánica es una de las causas más frecuentes de ingreso de los pacientes en UCI. Entre las etiologías más frecuentes se encuentran la reagudización de la enfermedad pulmonar obstructiva crónica y la insuficiencia respiratoria aguda con lesión pulmonar aguda o con criterios de síndrome de distrés respiratorio agudo. Estos pacientes presentan un riesgo elevado de desnutrición por su enfermedad de base, por la situación catabólica en la que se encuentran y por el empleo de la ventilación mecánica. Ello justifica que estos pacientes deban ser valorados desde el punto de vista nutricional y que el uso de soporte nutricional especializado sea necesario. El soporte nutricional especializado debe paliar los efectos catabólicos de la enfermedad, evitar la sobrecarga de calorías y utilizar, en casos seleccionados, dietas específicas enriquecidas con ácidos grasos w-3 y antioxidantes que podrían mejorar el pronóstico (AU)

Severe acute respiratory failure requiring mechanical ventilation is one of the most frequent reasons for admission to the intensive care unit. Among the most frequent causes for admission are exacerbation of chronic obstructive pulmonary disease and acute respiratory failure with acute lung injury (ALI) or with criteria of acute respiratory distress syndrome (ARDS). These patient s have a high risk of malnutrition due to the under lying disease, their altered catabolism and the use of mechanical ventilation. Consequently, nutritional evaluation and the use of specialized nutritional support are required. This support should alleviate the catabolic effects of the disease, avoid calorie overload and, in selected patients, to use omega-3 fatty acid- and antioxidant-enriched diets, which could improve outcome (AU)

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Respiratory failure / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: Insuficiencia respiratoria

Severe acute respiratory failure requiring mechanical ventilation is one of the most frequent reasons for admission to the intensive care unit. Among the most frequent causes for admission are exacerbation of chronic obstructive pulmonary disease and acute respiratory failure with acute lung injury (ALI) or with criteria of acute respiratory distress syndrome (ARDS). These patients have a high risk of malnutrition due to the underlying disease, their altered catabolism and the use of mechanical ventilation. Consequently, nutritional evaluation and the use of specialized nutritional support are required. This support should alleviate the catabolic effects of the disease, avoid calorie overload and, in selected patients, to use omega-3 fatty acid and antioxidant-enriched diets, which could improve outcome (AU)

La insuficiencia respiratoria aguda grave que precisa ventilación mecánica es una de las causas mas frecuentes de ingreso de los pacientes en UCI. Entre las etiologías mas frecuentes se encuentran la reagudización de la enfermedad pulmonar obstructiva crónica y la insuficiencia respiratoria aguda con lesion pulmonar aguda o con criterios de síndrome de distrés respiratorio agudo. Estos pacientes presentan un riesgo elevado de desnutrición por su enfermedad de base, por la situación catabólica en la que se encuentran y por el empleo de la ventilación mecánica. Ello justifica que estos pacientes deban ser valorados desde el punto de vista nutricional y que el uso de soporte nutricional especializado sea necesario. El soporte nutricional especializado debe paliar los efectos catabólicos de la enfermedad, evitar la sobrecarga de calorías y utilizar, en casos seleccionados, dietas especificas enriquecidas con ácidos grasos ω-3 y antioxidantes que podrían mejorar el pronostico (AU)

[Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): respiratory failure]. / Recomendaciones para el soporte nutricional y metabólico especializado del paciente crítico. Actualización. Consenso SEMICYUC-SENPE: insuficiencia respiratoria.

Severe acute respiratory failure requiring mechanical ventilation is one of the most frequent reasons for admission to the intensive care unit. Among the most frequent causes for admission are exacerbation of chronic obstructive pulmonary disease and acute respiratory failure with acute lung injury (ALI) or with criteria of acute respiratory distress syndrome (ARDS). These patients have a high risk of malnutrition due to the underlying disease, their altered catabolism and the use of mechanical ventilation. Consequently, nutritional evaluation and the use of specialized nutritional support are required. This support should alleviate the catabolic effects of the disease, avoid calorie overload and, in selected patients, to use omega-3 fatty acid- and antioxidant-enriched diets, which could improve outcome.

Effects of hydroxyethyl starch resuscitation on extravascular lung water and pulmonary permeability in sepsis-related acute respiratory distress syndrome.

OBJECTIVE: Hydroxyethyl starch (HES) has greater volume expansion effect and longer intravascular persistence than crystalloids. HES also decreases microvascular permeability and capillary leakage by biophysically plugging endothelial leaks, exerting an anti-inflammatory effect, and decreasing activation of endothelial cells. The aim of our study was to determine whether medium molecular weight HES (pentastarch) resuscitation in the early stage of acute respiratory distress syndrome (ARDS) simultaneously increases cardiac output without worsening pulmonary edema and whether it attenuates pulmonary vascular permeability. DESIGN: Prospective observational study. SETTING: Twenty-bed medical intensive care unit of a tertiary medical center. PATIENTS: Twenty patients with early-stage ARDS. INTERVENTION: Volume expansion with a 500-mL infusion of 10% pentastarch (HES 200/0.5) at a rate of 10 mL/kg/hr. MEASUREMENTS AND MAIN RESULTS: Baseline hemodynamics including systemic and pulmonary artery blood pressures, central venous pressure, pulmonary artery occlusion pressure, and cardiac output were obtained from an online HP Component Monitoring System and a pulmonary artery catheter. Intrathoracic blood volume (ITBV), global end-diastolic volume, extravascular lung water (EVLW), and pulmonary vascular permeability (EVLW/ITBV) were measured with a PiCCOplus monitor. Hemodynamic measurements were repeated immediately and 2, 4, and 6 hours after volume expansion. Pentastarch loading significantly increased central venous pressure, pulmonary artery occlusion pressure, pulmonary arterial pressures, and cardiac output. Pulmonary mechanics, venous admixtures, and EVLW values remained unchanged throughout the study. EVLW/ITBV significantly decreased immediately after the pentastarch infusion. CONCLUSIONS: In patients with early ARDS, pentastarch resuscitation significantly improved their hemodynamics and cardiac output without worsening pulmonary edema and pulmonary mechanics. It even attenuated pulmonary vascular permeability.

An evaluation of the safety and efficacy of an anti-inflammatory, pulmonary enteral formula in the treatment of pediatric burn patients with respiratory failure.

Respiratory failure is associated with a high mortality rate in burned children. Recently, a specialized pulmonary enteral formula (SPEF) was commercially introduced as an adjunct intervention in acute lung injury management. SPEF contains condition-specific nutrients to modulate the inflammatory response. The study examined SPEF impact in critically ill, pediatric burn patients with respiratory failure. Medical records of acute burn patients admitted December 1997 to October 2006 were reviewed for SPEF treatment. Respiratory and renal indices were compared on the first and final days of SPEF use. Nineteen patients with respiratory failure received SPEF for a mean of 10.8 +/- 0.9 days during their acute burn course. Mean age was 5.3 +/- 1.5 years. Mean total body surface area burn was 44.3 +/- 5.4% with 32.5 +/- 6.4% full thickness. Patients were admitted 2.3 +/- 0.9 days postburn. Significant improvements in peak pressure, PEEP, FiO2, P:F ratio, Pco2, Po2, and ETco2 were noted. Seventeen of the 19 patients survived despite the fact that 9 of the 19 patients developed severe barotrauma requiring multiple tube thoracotomies, and all 19 had extremely poor prognoses at SPEF initiation. Adult SPEF formula for critically ill, pediatric burn patients with respiratory failure is safe and well tolerated. SPEF seems to facilitate recovery from acute lung injury as evidenced by improvements in oxygenation and pulmonary compliance.

Acute respiratory distress syndrome associated with hypercalcemia without parathyroid disorders.

Acute lung injury (ALI) can be induced by various causes. The occurrence of ALI associated with hypercalcemia has rarely been reported and the mechanisms are unknown. In the present study, we reported the clinical manifestation and pathological findings in patients with hypercalcemia and metastatic calcification. In addition, we addressed the possible mechanism and the preventive strategy for the acute episode of ALI due to hypercalcemic crisis. We encountered five patients with long-term malignancy of various origins. They displayed hypercalcemia and metastatic calcification in the kidney and stomach. One case with transitional cell carcinoma of the urinary bladder developed acute episode of acute respiratory distress syndrome (ARDS). The plasma calcium was elevated to above 5 mM. Simultaneously, He manifested ARDS followed by ALI. The pathological examination revealed severe alveolar edema with multiple calcification. In the other three cases, the plasma calcium level ranged from 3.1 to 4.4 mM and ARDS or ALI did not occur. One patient with esophageal squamous cell carcinoma experienced an acute hypercalcemia (plasma calcium 4.8-5.1 mM) accompanied by ARDS. Corticosteroid and calcitonin were prescribed to reduce the plasma calcium. The symptoms of ARDS also subsided and ALI did not occur. Chronic hypercalcemia results in severe metastatic calcification. The kidney and stomach are the most vulnerable organs. An increase in plasma calcium above 5 mM is a risk factor for developing ARDS and ALI. Our recent experiment in conscious rats and isolated rat's lungs supported this contention. In addition, corticosteroid and calcitonin were able to reduce the plasma calcium and to prevent the occurrence of ARDS and ALI.