Factors Underlying the Early Limb Muscle Weakness in Acute Quadriplegic Myopathy Using an Experimental ICU Porcine Model

The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications

Diaphragm Muscle Weakness in an Experimental Porcine Intensive Care Unit Model

In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit

Intralymphatic Immunotherapy : A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen

Allergy to pollen and animal dander is a major public health problem. Close to 30% of the population have symptoms from the upper and/or lower respiratory tract when they meet fur animals or pollen. Whereas symptom-relieving medications have a good to sufficient effect on about 80% of those affected, a large group of 10–20% have severe symptoms, despite medication, with an impact on well-being and ability to work. In Sweden, the annual cost of allergy was calculated at €1.3 billion in 2014. Immunotherapy is effective in treating and preventing pollen allergy and allergic asthma, but is expensive, complicated, requiring 40 injections, and takes more than three years to complete if subcutaneous injections are used. Tablets placed under the tongue are another method, with one tablet taken every day for three years. Only 1.5‰ receive such treatment, yet just over 3% would need it. With intralymphatic immunotherapy, a small dose of allergen is given in a lymph node in the groin on 3 occasions, one month apart. As this method takes only eight weeks, it is a much faster and less costly treatment. However, although several studies have shown that the treatment is safe, its efficacy remains the subject of doubt. Our pilot study in 2012, with a 3-year follow-up to 2015, showed encouraging results, and was followed by a double-blind randomised study with 72 participants from 2014 to 2018. The research subjects then received treatment with birch and grass pollen extract or one extract and a placebo. Regardless of treatment, symptoms, quality of life and medication consumption improved during the birch and grass pollen seasons in the 3 years after treatment. Increased frequencies of T-regulatory lymphocytes may explain the non-specific effects. In 2017 to 2018, we conducted a double-blind study with 38 participants, half of whom received placebo and half, active treatment. In this study, we saw no difference between the treatment groups in the first year after treatment. However, after discontinuation and unblinding in 2019, i.e., two years after treatment, the actively treated group improved in terms of symptoms, and quality of life was improved compared with the placebo group despite less need for medication. T-regulatory lymphocytes increased one year after treatment only in the actively treated group. A long-term follow-up of the research subjects from our two larger studies in 2022, i.e., five to eight years after treatment, showed in the double-blind study without a pure placebo that the scores for symptoms, medication use, and quality of life remained as low as after the first three years. In the placebo-controlled study, a statistically significant improvement in symptoms remained during the grass pollen season. Analysing the two studies together, symptom improvement was significant even during the birch pollen season. Thus, although the effect does not seem to diminish, those who did not receive birch, but only grass, needed to use more medication during the birch pollen season in 2022, seven to eight years after treatment. Moreover, those who did not receive grass but only birch needed more medication during the grass pollen season. This may suggest that the non-specific effect begins to wane after seven to eight years. Allergy to pollen is a major problem for individuals and society, where symptom-relieving treatment with drugs is not enough for many. They can be helped with immunotherapy, which takes at least three years, is expensive and fraught with side effects. In contrast, intralymphatic immunotherapy involves three injections over eight weeks. Our three studies show that the treatment is safe and indicate that it has a clinical effect up to eight years after treatment. T-regulatory cells appear to be important to the immunological mechanism, leading to tolerance to pollen.Funding agencies: Region Östergötland, the Allergy Center in Linköping, the Medical Research Council of Southeast Sweden (FORSS), the Th Bergh Foundation and the Asthma and Allergy Association</p

Astma lathund : Astma hos vuxna

Åtta till tio procent av den vuxna befolkningen har astma. Av dessa har 65 procent lindrig, 25 procent medelsvår och 10 procent svår astma. Astma är en heterogen sjukdom, där en kronisk luftvägsinflammation oftast föreligger. Sjukdomen kännetecknas av återkommande luftvägssymtom såsom pip i bröstet, andnöd, trånghetskänsla i bröstet och hosta som varierar över tiden tillsammans med en variabel luftvägsobstruktion

Astma lathund : Astma hos vuxna

Åtta till tio procent av den vuxna befolkningen har astma. Av dessa har 65 procent lindrig, 25 procent medelsvår och 10 procent svår astma. Astma är en heterogen sjukdom, där en kronisk luftvägsinflammation oftast föreligger. Sjukdomen kännetecknas av återkommande luftvägssymtom såsom pip i bröstet, andnöd, trånghetskänsla i bröstet och hosta som varierar över tiden tillsammans med en variabel luftvägsobstruktion

Astma lathund : Astma hos vuxna

Åtta till tio procent av den vuxna befolkningen har astma. Av dessa har 65 procent lindrig, 25 procent medelsvår och 10 procent svår astma. Astma är en heterogen sjukdom, där en kronisk luftvägsinflammation oftast föreligger. Sjukdomen kännetecknas av återkommande luftvägssymtom såsom pip i bröstet, andnöd, trånghetskänsla i bröstet och hosta som varierar över tiden tillsammans med en variabel luftvägsobstruktion

Astma lathund : Astma hos barn

Eftersom få läkemedelsstudier utförs på barn är många av dagens läkemedel som ges till barn ofullständigt dokumenterade vad gäller dosering, effekt och säkerhet. Barn får många läkemedel utanför godkänd produktresumé (off-label), som licensläkemedel eller som apoteksberett läkemedel. I brist på vetenskaplig dokumentation har barnläkarna tvingats att utveckla egna behandlingsrekommendationer som vilar på beprövad erfarenhet. Det gör att det kan föreligga skillnader mellan riktlinjer både på lokal och på nationell nivå. Vidare är diagnostiken svårare eftersom lungfunktionstester inte är möjligt på små- och förskolebarn. Våra rekommendationer vilar på referenserna sist i denna lathund

Astma lathund : Astma hos barn

Eftersom få läkemedelsstudier utförs på barn är många av dagens läkemedel som ges till barn ofullständigt dokumenterade vad gäller dosering, effekt och säkerhet. Barn får många läkemedel utanför godkänd produktresumé (off-label), som licensläkemedel eller som apoteksberett läkemedel. I brist på vetenskaplig dokumentation har barnläkarna tvingats att utveckla egna behandlingsrekommendationer som vilar på beprövad erfarenhet. Det gör att det kan föreligga skillnader mellan riktlinjer både på lokal och på nationell nivå. Vidare är diagnostiken svårare eftersom lungfunktionstester inte är möjligt på små- och förskolebarn. Våra rekommendationer vilar på referenserna sist i denna lathund

Astma lathund : Astma hos barn

Eftersom få läkemedelsstudier utförs på barn är många av dagens läkemedel som ges till barn ofullständigt dokumenterade vad gäller dosering, effekt och säkerhet. Barn får många läkemedel utanför godkänd produktresumé (off-label), som licensläkemedel eller som apoteksberett läkemedel. I brist på vetenskaplig dokumentation har barnläkarna tvingats att utveckla egna behandlingsrekommendationer som vilar på beprövad erfarenhet. Det gör att det kan föreligga skillnader mellan riktlinjer både på lokal och på nationell nivå. Vidare är diagnostiken svårare eftersom lungfunktionstester inte är möjligt på små- och förskolebarn. Våra rekommendationer vilar på referenserna sist i denna lathund